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  • 1
    Electronic Resource
    Electronic Resource
    Control of cardiomyocyte gene expression as drug target (2000)
    Springer
    Molecular and cellular biochemistry 212 (2000), S. 135-142 
    Details
    ISSN: 1573-4919
    Keywords: gene expression ; catecholamines ; angiotensin II ; heart failure ; myosin ; hypertension ; eprosartan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Pressure overload of the heart is associated with a perturbed gene expression of the cardiomyocyte leading to an impaired pump function. The ensuing neuro-endocrine activation results in disordered influences of angiotensin II and catecholamines on gene expression. To assess whether angiotensin II type 1 receptor inhibition can also counteract a raised sympathetic nervous system activity, spontaneously hypertensive rats fed a hypercaloric diet were treated with eprosartan (daily 90 mg/kg body wt) and cardiovascular parameters were monitored with implanted radiotelemetry pressure transducers. Both, blood pressure and heart rate were increased (p 〈 0.05) by the hypercaloric diet. Although eprosartan reduced (p 〈 0.05) the raised systolic and diastolic blood pressure, the diet-induced rise in heart rate was blunted only partially. In addition to drugs interfering with the enhanced catecholamine influence, compounds should be considered that selectively affect cardiomyocyte gene expression via 'metabolic' signals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007181626766
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  • 2
    Electronic Resource
    Electronic Resource
    Angiotensin II-induced changes in G-protein expression and resistance of renal microvessels in young genetically hypertensive rats (2000)
    Springer
    Molecular and cellular biochemistry 212 (2000), S. 121-129 
    Details
    ISSN: 1573-4919
    Keywords: angiotensin II ; SHR ; preglomerular arterioles ; G-proteins ; cAMP ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Altered regulation of cAMP may contribute to enhanced renal reactivity to angiotensin II (Ang II) in spontaneously hypertensive rats (SHR). Such a phenomenon may occur in renal preglomerular arterioles and may involve changes in expression of GTP-binding regulatory proteins. We have examined the effects of Ang II on steady state levels of Gαi-1,2, Gαi-3 Gαs and Gαq in preglomerular arterioles from young marginally hypertensive SHR and on mean arterial pressure (MAP), renal vascular resistance (RVR) and renal cAMP excretion (UcAMP.V). Young (5-6 week old) SHR and Wistar Kyoto (WKY) rats received Ang II (35 ng/kg/min, s.c.) or vehicle for 7 days via osmotic minipumps. Urine was collected over the last 24 h. On day seven, MAP and renal blood flow were measured in anesthetized rats and RVR was determined. Preglomerular arterioles were isolated by perfusing the kidneys with iron oxide and using a series of mechanical steps coupled with the use of a magnet to retain iron-laden vessels. Membranes were prepared and the expressions of Gαi-1,2, Gαi-3, Gαs and Gαq were evaluated by Western immunoblotting. Baseline MAP (124 ± 6 mmHg) was only marginally (p 〉 0.05) higher in SHR when compared with WKY rats (110 ± 4 mmHg). RBF (3.04 ± 0.16 mL/min) was significantly lower and RVR (41.10 ± 1.37 mmHg.min/mL) was significantly higher in SHR when compared to age-matched WKY rats (4.36 ± 0.30 mL/min and 25.79 ± 1.58 mmHg.min/mL, respectively). Ang II significantly increased MAP in SHR (17 mmHg) but not in WKY rats. These increases in MAP were accompanied by significant increases in RVR in SHR (48% over control) but not in WKY rats. Compared to WKY rats, preglomerular arterioles from SHR exhibited significantly higher basal expression of Gαi-1,2 (11- fold), Gαi-3 (13-fold) and Gαs (3-fold). Chronic infusion of Ang II, however, downregulated the expression of Gαs (by 53%; p 〈 0.05), Gαi-1,2 ( by 72%; p 〈 0.05) and Gαi-3 (by 35%; p 〉 0.05) in SHR preglomerular arterioles but significantly upregulated the expression of these proteins in WKY by 3-, 8- and 15-fold, respectively. Basal levels of Gαq were not different in preglomerular arterioles from the two strains but were downregulated by Ang II in both WKY (74% of basal) and SHR (52% of control). Baseline UcAMP.V was significantly lower in SHR (31.22 ± 6.51 nmol/24 h) compared with WKY rats (65.33 ± 3.60 nmol/24 h). Chronic Ang II infusion significantly increased UcAMP.V in SHR as well as WKY rats. These data clearly demonstrate that expressions of Gi isoforms as well as Gs in renal microvessels are elevated during early stages of hypertension and suggest that the elevated levels of Gi proteins may be directly associated with a blunted adenylyl cyclase-cAMP cascade in the renal microvasculature. Furthermore, Ang II appears to directly downregulate the expression of Gs in young SHR but not in young WKY renal microvessels. Such diversity in its effect on G-protein expression may be important for enhanced renal sensitivity to Ang II in SHR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007125525858
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  • 3
    Electronic Resource
    Electronic Resource
    Designing antisense to inhibit the renin-angiotensin system (2000)
    Springer
    Molecular and cellular biochemistry 212 (2000), S. 145-153 
    Details
    ISSN: 1573-4919
    Keywords: angiotensin ; antisense ; oligodeoxynucleotide ; plasmid ; adeno-associated virus ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Overactive renin-angiotensin system has been indicated in numerous pathological situations. Current treatment is based on pharmaceutical compounds, which work on the proteins level. Undisputedly helpful, it is not, however, flawless. Some of the drawbacks include adverse effects and non-compliance problem, since in many cases medicine has to be taken at least once a day for a long time. Therefore it seems logical to try a different approach, for instance to correct the disease at the gene expression level, possibly having a choice of shorter or longer-lasting effects. This current review combines results, relevant to the angiotensin system, with the antisense approach, which decreases amount of target protein by interfering at the mRNA level. Dependent on the tool used - oligodeoxynucleotide, plasmid or viral vector, the antisense effect lasts from few days to months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007192624989
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  • 4
    Electronic Resource
    Electronic Resource
    Age-related difference in cardiac adaptation to chronic hypertension in rats, with and without nifedipine treatement (1999)
    Springer
    Molecular and cellular biochemistry 198 (1999), S. 109-112 
    Details
    ISSN: 1573-4919
    Keywords: LVH ; hypertension ; aging ; myosin isozyme ; nifedipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Three myosin isozymes, V1 (αα MHC = Myosin Heavy Chain gene), V2 (αβ MHC) and V3 (ββ MHC) that are identified in the cardiac ventricles of most mammals have been shown to shift to a V3 predominance pattern during cardiac growth and in response to left ventricular pressure overload, and to V1 predominance following anti hypertensive treatment. This study examined whether long-term hypertension impairs the ability of the adult heart to restructure myosin isozyme proportions. Using pyrophosphate gel electrophoresis, we studied proportions of cardiac myosin isozymes (V1 and V3) in young (16 weeks) and adult (36 weeks) spontaneously hypertensive rats (SHR), and following 12 weeks of nifedipine (N) treatment in age-matched SHR rats (SHR-N). The values of V1 and V3 myosin isozymes were derived by adding half of the value of V2 to each isozyme proportion. The V3 proportion in the young SHR control (SHR-C) group (49%) was 34% higher (p 〈 0.05) than in the young Wistar Kyoto control (WKY-C) group (37%). However, the proportion was similarly high, though not statistically significant, in both the adult SHRC (73%) and WKY-C (71%) groups. The proportion in the young SHR-N group (29%) was 41% lower (p 〈 0.05) than in the young SHR-C group (49%), and the proportion in the adult SHR-N group (47%) was 34% lower (p 〈 0.05) than in the adult SHR-C group (73%). The ratio of left ventricular weight to body weight (LVW/BW), which determines left ventricular hypertrophy (LVH), was higher in both young and adult SHR-C (26%, p 〈 0.05, and 42%, p 〈 0.05, respectively) than in WKY-C groups. The mean LVW/BW was 27% (p lt; 0.05) greater in adult than in young SHR-C rats. The LVW/BW in both age groups of treated SHR-N was similar to that in age matched WKY-C rats. Conclusion: Our study showed that a rise in the V3 level occurs in young hypertensive rats, but no rise occurs in the V3 level in adult hypertensive rats. High blood pressure seems to contribute to the high V3 level in young hypertensive rats, but in adult hypertensive rats, high blood pressure does not accentuate the V3 rise already acquired due to the aging process. Nifedipine treatment in both young and adult hypertensive rats prevented the V3 rise due to hypertension and to the aging process. This effect of nifedipine seems to be through its antihypertensive action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006968011206
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  • 5
    Electronic Resource
    Electronic Resource
    Changes of sodium and ATP affinities of the cardiac (Na,K)-ATase during and after nitric oxide deficient hypertension (1999)
    Springer
    Molecular and cellular biochemistry 202 (1999), S. 141-147 
    Details
    ISSN: 1573-4919
    Keywords: (Na,K)-ATPase ; Na+-binding site ; nitric oxide ; hypertension ; L-NAME ; cardiac sarcolemma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day NG-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the KNa increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The KNa value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity. (Mol Cell Biochem 000: 000-000, 1999)
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007097617502
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  • 6
    Electronic Resource
    Electronic Resource
    Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats (1999)
    Springer
    Molecular and cellular biochemistry 200 (1999), S. 155-162 
    Details
    ISSN: 1573-4919
    Keywords: aldehydes ; vitamin B6 ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels, increasing cytosolic free calcium and blood pressure. N-acetyl cysteine normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. It is known that dietary vitamin B6 supplementation can increase the level of endogenous cysteine. Our objective was to investigate whether a dietary supplementation of vitamin B6 can prevent hypertension and associated changes in SHRs. Starting at 7 weeks of age, animals were divided into three groups of six animals each. Animals in WKY-control group and SHR-control group were given a normal vitamin B6 diet; and SHR-vitamin B6 group, a high vitamin B6 diet (20 times the recommended dietary intake; RDA) for the next 14 weeks. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls compared to WKY controls. These animals also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation attenuated the increase in systolic blood pressure, tissue aldehyde conjugates and associated changes. These results further support the hypothesis that aldehydes are involved in increased systolic blood pressure in SHRs and suggest that vitamin B6 supplementation may be an effective antihypertensive.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007088512834
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  • 7
    Electronic Resource
    Electronic Resource
    Antihypertensive effect of low ethanol intake in spontaneously hypertensive rats (1999)
    Springer
    Molecular and cellular biochemistry 200 (1999), S. 85-92 
    Details
    ISSN: 1573-4919
    Keywords: ethanol ; aldehydes ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Light to moderate drinking in humans lowers the risk of coronary heart disease and may lower blood pressure. We examined the effect of chronic low daily alcohol consumption on blood pressure, platelet cytosolic free calcium [Ca2+]i, tissue aldehyde conjugates and renal vascular changes in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). We also examined the effects of the same weekly amount of alcohol consumption over a one day period each week simulating weekend drinking in humans. Animals, age 7 weeks, were divided into six groups of six animals each and were treated as follows: WKY and SHR control, normal drinking water; WKY and SHR, 0.5% ethanol in drinking water; WKY and SHR, 3.5% ethanol in drinking water one day/week. After 14 weeks systolic blood pressure, platelet [Ca2+]i, liver, kidney and aortic aldehyde conjugates were significantly higher (p 〈 0.05) in untreated SHRs as compared to untreated WKYs. Daily 0.5% ethanol consumption in SHRs significantly (p 〈 0.05) attenuated these changes and also attenuated smooth muscle cell hyperplasia and narrowing of the lumen in small arteries and arterioles of the kidney. WKY rats treated with 0.5% ethanol had lower aldehyde conjugates without any significant effect on blood pressure and platelet [Ca2+]i as compared to WKY controls. Consumption of 3.5% ethanol one day/week did not affect blood pressure and associated changes in normotensive WKY rats or hypertensive SHRs as compared to their respective controls. These results suggest that chronic daily low ethanol intake lowers blood pressure in SHRs by lowering tissue aldehyde conjugates and cytosolic free calcium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006950414560
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  • 8
    Electronic Resource
    Electronic Resource
    Myocardial hypertropy in rabbits with renovascular hypertension under pharmacological blockade of angiotensin II synthesis and its interaction with specific receptors (1999)
    Springer
    Bulletin of experimental biology and medicine 127 (1999), S. 457-459 
    Details
    ISSN: 1573-8221
    Keywords: hypertension ; treatment ; myocardial hypertrophy ; regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The dynamics of blood pressure, the weight of the heart and its subdivisions, and morphology of myocardium were studied in the rabbits with experimental renovascular hypertension. Treatment with inhibitors of angiotensin II synthesis (lotensin) or its interaction with specific receptors (valsartan) decreased blood pressure and the weight of the left ventricle, but did not affect the interrelations between structural elements in the heart, which remained the same as in hypertension-induced myocardial hypertrophy. In addition, these drugs impaired some parameters of cardiac activity attesting to myocardial overload, increase in collagen content in the myocardium, and decrease in the ratio of the numbers of capillaries and mitochondria to the weight of myofibrils.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02434937
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  • 9
    Electronic Resource
    Electronic Resource
    Effects of enalapril on cerebral blood flow and its autoregulation in hypertensive rats (1999)
    Springer
    Bulletin of experimental biology and medicine 127 (1999), S. 584-586 
    Details
    ISSN: 1573-8221
    Keywords: enalapril ; hypertension ; cerebral blood flow ; autoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lower limit of cerebral blood flow autoregulation was shifted to a higher blood pressure in rats with renal and spontaneous hypertension. Enalapril decreased blood pressure and vascular resistance in the brain, stabilized cerebral blood flow, and potentiated autoregulatory response of cerebral vessels to blood pressure drop.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02433284
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  • 10
    Electronic Resource
    Electronic Resource
    Morphological peculiarities of juxtaglomerular apparatus of the kidney in rats with hereditary stress-induced arterial hypertension (NISAG rats) (1999)
    Springer
    Bulletin of experimental biology and medicine 127 (1999), S. 522-525 
    Details
    ISSN: 1573-8221
    Keywords: heredity ; stress ; hypertension ; kidneys ; juxtaglomerular apparatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Structure of juxtaglomerular apparatus of the kidney in NISAG rats and morphometric parameters of renin-producing juxtaglomerular, cells of afferent arterioles attest to its activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02434958
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  • 11
    Electronic Resource
    Electronic Resource
    Nutritional and endocine modulation of intracellular calcium: Implications in obesity, insulin resistance and hypertension (1998)
    Springer
    Molecular and cellular biochemistry 188 (1998), S. 129-136 
    Details
    ISSN: 1573-4919
    Keywords: agouti calcium ; insulin resistance ; hypertension ; obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Regulation of intracellular Ca2+ ([Ca2+]i) plays a key role in obesity, insulin resistance and hypertension, and [Ca2+]i disorders may represent a fundamental factor linking these three conditions. We have shown insulin to be a direct vasodilator, attenuating voltage-gated Ca2+ influx and stimulating Ca2+-ATPase transcription via a glucose-6-phosphate response element. These result in a net decrease in [Ca2+]i and thereby decrease vascular resistance, while these effects are blunted in insulin resistance, leading to increased vascular resistance. Consistent with this concept, pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. While insulin regulates [Ca2+]i Ca2+ also regulates insulin signaling, as increasing [Ca2+]i impairs insulin signaling in some systems, possibly due to Ca2+ inhibition of insulin-regulated dephosphorylation. Finally, in recent studies of the mouse agouti gene, we have also demonstrated increased [Ca2+]i to play a key role in adipocyte lipogenesis, as follows. We have found dominant agouti mutants to exhibit increased [Ca2+]i in most tissues, leading to increased vascular reactivity and insulin resistance in vascular smooth muscle and skeletal muscle cells, respectively. Further, we have found recombinant agouti protein to directly increase [Ca2+]i in a variety of cells, including murine and human adipocytes, and to stimulate both the expression and activity of adipocyte fatty acid synthase and increase triglyceride accumulation in a Ca2+-dependent manner. These effects can be mimicked by stimulation of Ca2+ influx and blocked by Ca2+ channel inhibition, while treatment of mice with a Ca2+ antagonist attenuates agouti-induced obesity. Since humans express agouti in adipose tissue, it may similarly exert paracrine effects on [Ca2+]i and thereby stimulate de novo lipogenesis and promote obesity. Thus, Ca2+ signaling represents a target for therapeutic intervention in obesity as well as hypertension and insulin resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006880708475
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  • 12
    Electronic Resource
    Electronic Resource
    Hypertension, calcium channel and pyridoxine (vitamin B6) (1998)
    Springer
    Molecular and cellular biochemistry 188 (1998), S. 137-148 
    Details
    ISSN: 1573-4919
    Keywords: Ca2+ channels ; hypertension ; vitamin B6 ; vitamin deficiency ; Zucker rat ; vascular biology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The moderately pyridoxine (vitamin B6)-deficient male rat was introduced by us as an animal model (B6DHT) for the study of hypertension. Hypertension in this rat is associated with increased sympathetic stimulation. Arterial segments from B6DHT rats maintained a higher resting tone. The influx of 45calcium into intracellular compartment of the vascular smooth muscle of the caudate artery of B6DHT rats was also enhanced. Administration of pyridoxine attenuated the hypertension in B6DHT rats as well as in genetic or dietary-induced moderately hypertensive conditions such as in the Zucker obese rat and sucrose or low calcium-fed rats. However, pyridoxine did not have any effect or the spontaneously hypertensive rat. All classes of calcium channel blockers were effective in lowering the systolic blood pressure of B6DHT rats. The increased in vitro influx of45 calcium into intracellular compartment of artery segments of B6DHT rats as well as the BAY K 8644-induced influx of45 calcium into artery segments from normal rats were blocked by pyridoxal phosphate as well as by dihydropyridine-sensitive calcium channel blockers (DHP). Pyridoxal phosphate (PLP) in vitro enhances the binding of calcium channel antagonists to membrane preparations from vascular tissue. PLP corrects the membrane abnormality in responsive hypertensive conditions and thus, could be an endogenous modulator of DHP - sensitive calcium channels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006832810292
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  • 13
    Electronic Resource
    Electronic Resource
    Role of aldehydes in fructose induced hypertension (1998)
    Springer
    Molecular and cellular biochemistry 181 (1998), S. 1-9 
    Details
    ISSN: 1573-4919
    Keywords: fructose ; aldehydes ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Aldehydes are formed in tissues of humans and animals as intermediates of glucose and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals age 7 weeks were divided into three groups of 6 animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4% fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4% fructose in drinking water). After 11 weeks, systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose treated rats. NAC treatment prevented these changes. These results suggest that aldehydes may be the cause of fructose induced hypertension and elevated cytosolic free calcium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006844222963
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  • 14
    Electronic Resource
    Electronic Resource
    Plasma and lymph electrolyte and endocrine parameters in rats with genetically-determined arterial hypertension (1997)
    Springer
    Bulletin of experimental biology and medicine 124 (1997), S. 652-654 
    Details
    ISSN: 1573-8221
    Keywords: hypertension ; electrolytes ; hormones ; blood ; lymph
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Hemolymphatic interactions of electrolytes and plasma contents of aldosterone and insulin are studied in rats with genetically-determined stress-induced arterial hypertension (NISAG) and in normotensive rats (Wistar). Correlation analysis shows that alterations in electrolyte metabolism in NISAG are strongly determined by endocrine influences. These alterations are regarded, on the one hand, as a mechanism responsible for generically-determined arterial hypertension, and, on the other hand, as a variant of “adaptation disease” accompanied by transformation of primarily adaptive reactions into a pathogenic factor of arterial hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02445052
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  • 15
    Electronic Resource
    Electronic Resource
    Nonopioid nature of the pressor effect of FMRF-amide (1997)
    Springer
    Bulletin of experimental biology and medicine 124 (1997), S. 1072-1074 
    Details
    ISSN: 1573-8221
    Keywords: FMRFa ; opioids ; hypertension ; adrenoreceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The effect of the peptide FMRFa on arterial pressure, heart rate, and respiratory rate is examined in anesthetized rats. It is demonstrated that the effect of FMRFa is similar to that of epinephrine and is characterized by transient hypertension against the background of bradycardia and decreased respiratory rate followed by hypotensive phase. Opiate antagonists and agonists do not modify the effect of FMRFa. Pressor effect of FMRFa is inhibited by Aminazine and is abolished by dihydroergotamine, while clopheline, reserpine, propranolol, Dimedrol, and adrenalectomy have no appreciable effect on it. It is suggested that the effects of FMRFa are realized via vascular adrenoreceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02445664
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  • 16
    Electronic Resource
    Electronic Resource
    How informed general practitioners manage mild hypertension: a survey of readers of drug bulletins in 7 countries (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 445-450 
    Details
    ISSN: 1432-1041
    Keywords: Practioners ; hypertension ; general practice ; disease management ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To determine whether general practitioners (GP) who are readers of independent drug bulletins can be used as an international epidemiological observatory of the criteria adopted by “well informed” doctors in various countries in the management of mild hypertension. Design: Questionnaire study of GPs' diagnostic criteria for mild hypertension, routine investigation and management of patients with this diagnosis. Participants: 206 GPs readers of independent drug bulletins in 7 countries, comprising 95 known systematic readers of a local bulletin and 111 randomly selected regular subscribers. Main outcome measures: Response rate to the questionaire. Diagnostic criteria, routine investigations, and treatment used for patients with mild hypertension. Results: The study required two months for planning and implementation. Four countries out of eleven had a response rate ≤50% and were excluded; the frequency of responses from other countries was 69%. The average diastolic blood pressure (DBP) considered diagnostic of mild hypertension range from 94 mm Hg (lower threshold) to 106 (upper threshold). A minority (17%) of GPs routinely request the minimum recommended laboratory tests to assess patients. GPs routinely advise non-drug measures before starting a drug. Most would not start drug treatment in patients without other risk factors and a DBP below 100 mmHg. The top first choice drugs were diuretics and β-adrenoceptor blockers. Half of the doctors were able to quote some published guide to the management of mild hypertension, and 18% cited a relevant trial. Attitudes in diagnosing and treating mild hypertension differed widely between GPs and countries. Conclusions: GP readers of drug bulletins can be used quickly and inexpensively to assess the extent to which recommended diagnostic and therapeutic practices are accepted by “well informed” doctors. The results suggest that attitudes in managing mild hypertension vary widely among GPs and countries and differ remarkably from the recommendations of published guidelines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195929
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  • 17
    Electronic Resource
    Electronic Resource
    Estrogen effects in the heart (1996)
    Springer
    Molecular and cellular biochemistry 160-161 (1996), S. 307-313 
    Details
    ISSN: 1573-4919
    Keywords: myocardium ; hypertension ; gene expression ; estrogens ; cardiac hypertrophy ; signal transduction ; genetic program
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Gender specific differences in cardiovascular disease are largely mediated by sex hormones. The use of estrogens significantly reduces the overall incidence of heart disease in postmenopausal women. Beneficial effects of estrogens on plasma lipoprotein levels are clearly established. However, these do not explain the magnitude of risk reduction seen in clinical studies. Thus, additional and currently unknown functions of estrogens must be operative. Elucidation of the exact estrogen action in the heart will have important implications in the treatment of cardiovascular disease. It will probably enhance the therapeutic repertoire in treating heart disease, the most common cause of death in industrialized countries. We will review the current understanding of the function of estrogens in the heart and discuss potential strategies on how to apply these data to clinical practice.
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    URL: http://dx.doi.org/10.1007/BF00240064
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    Reduction of cardiac hypertrophy in TGR(mREN2)27 by angiotensin II receptor blockade (1996)
    Springer
    Molecular and cellular biochemistry 163-164 (1996), S. 217-221 
    Details
    ISSN: 1573-4919
    Keywords: heart hypertrophy ; transgenic rats ; hypertension ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract TGR(mREN2)27 is a transgenic rat harboring the murine Ren-2 gene and exhibit fulminant hypertension and marked heart hypertrophy. In order to study the role of angiotensin II in the increase of cardiac mass, these animals were treated with anti-hypertensive and non-antihypertensive doses of the angiotensin II receptor AT1 antagonist Telmisartan for 9 weeks. All doses led to significant reductions of heart hypertrophy detected by the evaluation of the diameter of cardiac muscle bundles. We conclude from this study that cardiac hypertrophy in TGR(mREN2)27 is characterized by an increased volume of cardiomyocytes and an unchanged amount of fibrous tissue and that angiotensin II plays an important role in the mechanisms leading to this phenotype.
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    URL: http://dx.doi.org/10.1007/BF00408661
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    Plasma adenosine concentrations are elevated in Dahl salt-sensitive rats (1995)
    Springer
    Cellular and molecular life sciences 51 (1995), S. 227-229 
    Details
    ISSN: 1420-9071
    Keywords: Adenosine ; Dahl salt-sensitive rats ; high-performance liquid chromatography ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We measured plasma levels of adenosine in Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) to examine the potential role of adenosine in cardiovascular regulation in this type of hypertension. Plasma adenosine concentrations were significantly higher in DS than in DR. The NaCl content in the diet did not affect plasma adenosine concentration in either DS or DR. Significant positive correlation was found between adenosine concentrations and systolic blood pressure when the data for DS and DR were analyzed together. These results suggest that adenosine may play an important role in the pathophysiology of hypertension in DS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01931102
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    Patient compliance and therapeutic coverage: comparison of amlodipine and slow release nifedipine in the treatment of hypertension (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 477-481 
    Details
    ISSN: 1432-1041
    Keywords: Amlodipine ; Nifedipine ; Compliance ; slow release formulation ; hypertension ; therapeutic coverage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To study patient compliance in hypertensive outpatients amlodipine (5 mg once daily) and slow release nifedipine (20 mg twice daily) were compared in an open, crossover study in general practices. Four methods of assessment for patient compliance (pill count, taking compliance, days with correct dosing, timing compliance) were used in both study arms. For the latter three assessment a special device, the medication event monitoring system, was used to record the time and date of each opening and closure of the container. The compliance of the 320 hypertensive patients with once-daily amlodipine was markedly superior to twice-daily slow release nifedipine. Therapeutic coverage was also significantly better for amlodipine in the hypertensive patients. Amlodipine was better tolerated than nifedipine slow release. Patient compliance and therapeutic coverage with the calcium antagonist amlodipine given once daily was superior to slow release nifedipine b. d. in hypertensive outpatients recruited in general practice. Statistical Unit: Léon Kaufmann, Marie-Paule Derde, Data Investigation Company Europe, Brussels Participating Investigators: D. Abbate, G. Armand, C.I. Authelet, J.L. Badot, J. Baeck, P. Baeck, P. Bastin, C.I. Bernard, P. Bernard, B. Beyssens, J. Bosly, P. Boudart, J. Bourdeaudhuy, W. Callens, L. Carolides, Y. Catry, E. Cerstelotte, F. Charlier, H. Charloteaux, J.M. Chaudron, L. Christiaen, G. Cornette, P. Cranskens, R. Creteur, N. De Cock, M. De Corte, A. De Vos, P. Defrance, P. Delhaye, G. Deneckere, M. Dobbeleir, A. Dufour, P. Dumont, L. D'Haen, H. D'Haenens, P. Eloy, P. Evrard, C. Fellemans, G. Geeraerts, L. Gielen, D. Grand, J. Grosjean, J. Guffens, R. Guillaume, R. Hacquaert, V. Hamoir, W. Hens, M. Hondeghem, M.C. Humblet-Koch, L. Leven, W. Janssens, L. Jeanfils, J. Jodogne, B. Jortay, W. Ketels, J.M. Krzesinski, E. Langendries, J. Lannoy, M. Leeman, J. Leire, P. Lempereur, L. Lenaerts, F. Lustman, R. Martens, Y. Maus, M. Meroueh, J.P. Meurant, P. Meurant, A. Michiels, E. Mievis, H. Moors, K. Naesens, P. Neels, J. Neven, W. Odeurs, W. Pardon, M. Peduzzi, J. Piette, D. Plessers, P. Putzeys, A. Quoidbach, A. Renaerts, G. Rits, M. Ruhwiedel, M. Salavracos, M. Seret, P. Sibille, M. Taziaux, J. Teucq, H. Therasse, F. Tihon, F. Vandenput, J. Van Elsen, J.P. Van Liefferinge, J. Van Neck, M. Van Pelt, T. Van Vlaenderen, G. Vandenbeylaardt, M. Vandewoude, F. Veldeman, D. Ven, F. Verbruggen, A. Vlaeminck, P. Werion, J. Westerlinck.
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    URL: http://dx.doi.org/10.1007/BF00193697
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    Relationship between elevated lipid peroxides, vitamin E deficiency and hypertension in preeclampsia (1995)
    Springer
    Molecular and cellular biochemistry 151 (1995), S. 33-38 
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    ISSN: 1573-4919
    Keywords: preeclampsia ; vitamin E ; lipid peroxidation ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Preeclampsia or pregnancy-induced hypertension is a major cause of both maternal and fetal-neonatal morbidity and mortality. The deficiency of vitamin E can cause accumulation of lipid peroxidation products, which, in turn, can induce vasoconstriction. This study has examined any evidence of increased cellular lipid peroxidation and accumulation of malonydialdehyde (MDA, an end product of lipid peroxidation) in pregnancy-induced hypertension and any relationship between the elevated MDA and lower vitamin E levels with hypertension in pregnant women. EDTA-Blood was collected from pregnant women at the time of delivery. Plasma vitamin E was determined by HPLC; MDA by the thiobarbituric acid-reactivity. Subjects with diastolic blood pressure(DBP) ≥90 mm Hg were considered hypertensive (HT) and with 〈90 mm Hg normotensive (NT). Data (Mean±SE) from 49 NT and 11 HT women show that HT has significantly lower vitamin E (22±1 vs 27±1 nmole/ml, p〈0.03) and elevated MDA levels (0.56±0.06 vs 0.43±0.02 nmole/ml, p〈0.03) compared to NT; the ages and gestational ages of women were similar. Among all women, there was a significant positive relationship between DBP and MDA levels (r=0.27, p〈0.05), and a significant negative relationship between vitamin E levels and DBP (−0.36, p〈0.005), and a significant negative relationship between MDA and vitamin E levels (r=−0.27, p〈0.05). Thus, HT women's plasma has significantly lower E and higher MDA levels, and DBP significantly correlates with the extent of vitamin E deficiency and increased MDA levels. This study suggests a relationship between elevated lipid peroxidation and lower vitamin E levels and hypertension in pregnancy (preeclampsia).
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    URL: http://dx.doi.org/10.1007/BF01076893
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    Influence of spontaneous hypertension on n-3 delta-6-desaturase activity and fatty acid composition of rat hepatocytes (1995)
    Springer
    Molecular and cellular biochemistry 152 (1995), S. 7-12 
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    ISSN: 1573-4919
    Keywords: hepatocytes ; hypertension ; age ; desaturase ; essential fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The first and rate limiting step in the conversion of alpha-linolenic acid is catalyzed by the delta-6-desaturase enzyme. The activity of such an enzyme was studied in order to investigate the n-3 Polyunsaturated Fatty Acid biogenesis during hypertension. Rat isolated hepatocyte n-3 delta-6-desaturase activity was higher in 1 month old Spontaneously Hypertensive Rats — prehypertensive period- as compared to normotensive Wistar Kyoto rats, whereas there was no significant difference at 12 months — hypertensive period-. Our data indicate no correlation between the directly measured enzyme activity and the changes in hepatocyte n-3 fatty acid compositions. The loss of hepatocyte n-3 delta-6-desaturase activity in the Spontaneously Hypertensive Rat may be a key factor in the evolution of hypertension related to aging through altering the eicosanoid balance.
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    URL: http://dx.doi.org/10.1007/BF01076458
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    Heat shock protein 72 in cardiac and skeletal muscles during hypertension (1995)
    Springer
    Molecular and cellular biochemistry 146 (1995), S. 1-6 
    Details
    ISSN: 1573-4919
    Keywords: heat shock protein ; hypertension ; aging ; myocardium ; skeletal muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In order to elucidate the relationship between hypertension and hypertrophy in the production of heat shock proteins, we studied the induction of the HSP72 synthesis by the heart and gracilis muscles of normo (WKY) and hypertensive (SHR) rats subjected to hyperthermia (42°C±0.5 for 15 min). Two age groups were investigated in each strain: young (2 months, with developing cardiac hypertrophy) and old (18 months, with fully developed chronic cardiac hypertrophy). The gracilis muscle never developed hypertrophy, independently of hypertension or aging. 72 kDa inducible protein was determined by Western blot analysis using a specific monoclonal antibody. We also used a commercial standard, loaded on each blot, to quantitate densitometrically the signal. The heart of young SHR responds to heat shock more than their normotensive age-matched control (298.8±24.7% vs 88.3 ±8.5%, p〈0.001). This response is not maintained during aging as we did not find any significant difference between normo-and hypertensive old rats after exposure to hyperthermia (43.6±5.3% vs 65.3±10.4%). Unlike the heart, the gracilis muscle shows a basal spontaneous HSP72 synthesis in both the SHR (71.4±10.8%) and WKY (40.6±11.7%) animals. There was a significant increase in HSP72 synthesis in the gracilis muscle of young SHR with respect to their control (186.2±18.7% vs 115.8±9.9%, p〈0.02) which was maintained also during aging (171.9±17.3% vs 95.2±10.5%, p〈0.01). In conclusion, these data show that hypertension results in an increased synthesis of HSP72 both in cardiac and gracilis muscle in response to heat shock. This abnormal response is attenuated by aging in the heart but not in the gracilis muscle. Thus, the abnormality seems to be independent from hypertrophy and linked to genetic determination of the disease.
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    URL: http://dx.doi.org/10.1007/BF00926874
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    Increased potency of vanadium using organic ligands (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 175-180 
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    ISSN: 1573-4919
    Keywords: Vanadium ; diabetes ; insulin-mimetic ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Thein vivo glucose lowering effect of orally administered inorganic vanadium compounds in diabetes was first reported in our laboratory in 1985. While both vanadate and vanadyl forms of vanadium are orally active, they are still not well absorbed. We have synthesized several organic vanadium compounds and one compound, bis(maltolato)oxovanadium(IV) or BMOV, has been extensively investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic rats when administered in drinking water over a 25 week period. The maintenance dose (0.18 mmol/kg/day) was approximately 50% of that required for vanadyl sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also reduced blood glucose levels. The ED50 for BMOV was 0.5 mmol/kg, while for VS the estimated ED50 was 0.9 mmol/kg. BMOV was also effective by the intraperitoneal route in STZ-diabetic rats. The ED50 was 0.08 mmol/kg compared to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min period reduced plasma glucose levels by 50% while VS was not effective.
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    URL: http://dx.doi.org/10.1007/BF01075935
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    Antihypertensive effects of vanadium compounds in hyperinsulinemic, hypertensive rats (1995)
    Springer
    Molecular and cellular biochemistry 153 (1995), S. 205-209 
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    ISSN: 1573-4919
    Keywords: hyperinsulinemia ; insulin resistance ; hypertension ; vanadium compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Although considerable evidence lends credence to the association between insulin resistance, hyperinsulinemia and essential hypertension, the precise nature of this relationship remains unexplained. In the present investigation, we examined the proposition that these metabolic defects contribute causally to the development of high blood pressure. If these metabolic abnormalities were responsible for the development of hypertension, then drug interventions that improve these defects should also decrease high blood pressure. Since previous studies have demonstrated that vanadium compounds enhance insulin action and lower plasma insulin levels in nondiabetic rats, we examined the effects of these compounds on insulin sensitivity, plasma insulin concentration and blood pressure in two hyperinsulinemic models of experimental hypertension. The animal models studied were the genetically predisposed spontaneously hypertensive rat and the fructose-hypertensive rat, where hypertension is induced in normotensive rats by feeding them a high fructose diet. Vanadium compounds caused marked and sustained decreases in plasma insulin concentration and blood pressure in both the animal models studied. Furthermore, the effect of the drugs on blood pressure was reversed by restoring plasma insulin levels in the drug-treated rats to those observed in their untreated counterparts. These data suggest that either hyperinsulinemia contributes to the development of hypertension in both the spontaneously hypertensive and the fructose-hypertensive rats or that the underlying mechanism is closely related to the expression of both these disorders.
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    Nonactomyosin component of thermo-induced contractions of the vascular wall in hypertension (1995)
    Springer
    Bulletin of experimental biology and medicine 119 (1995), S. 28-31 
    Details
    ISSN: 1573-8221
    Keywords: vascular wall ; collagen ; nonactomyosin contractile mechanisms ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract It is determined that arterial hypertension induced by deoxycroticosterone results in the almost total disappearance of the nonactomyosin components of the thermomechanical responses of the thoracic section of the rat aorta wall. This may explain the known effect of the decreased mechanical stress generated by the vascular wall during hypertension. It is assumed that this decrease in the mechanical stress generated by nonactomyosin mechanisms is due to an increase in the conformational stability of collagen of the connective-tissue matrix.
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    URL: http://dx.doi.org/10.1007/BF02445922
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    Statistical evaluation of circadian blood pressure rhythm during isradipine long-term therapy (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 119-122 
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    ISSN: 1432-1041
    Keywords: Isradipine ; Fourier ; rhythm ; hypertension ; diurnal blood pressure rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In this study, using the two-step truncated Fourier series with four harmonics, we analysed the diurnal blood pressure profile in 13 mild-moderate essential hypertensive patients during isradipine long-term therapy. Circadian parameters such as the amplitudes and phases of the four harmonics and the overall amplitude and phase were obtained from the model. The total duration of the study was 26 weeks. Ambulatory blood pressure was measured at 15-min, intervals using a Takeda TM 2420 device after 2 weeks of placebo and after 6 and 26 weeks of isradipine (5 mg daily) respectively. After 6 and 26 weeks therapy the blood pressure values showed a significant decrease, although the daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by isradipine treatment. Both the night/day differences and the overall amplitude/acrophases were statistically significant at 0,6 and 26 weeks. According the nocturnal blood pressure fall, we found that long-term therapy with isradipine increased the number of patients with nocturnal blood pressure fall and reducing the early morning blood pressure rise. In conclusion, the two-step method Fourier analysis represents a novel and useful statistical approach to evaluate the presence of a significant diurnal blood pressure rhythm and to provide the circadian parameters of the 24-h blood pressure profile during pharmacological therapy.
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    URL: http://dx.doi.org/10.1007/BF00199873
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    Age-related changes in linoleic acid bioconversion by isolated hepatocytes from spontaneously hypertensive and normotensive rats (1994)
    Springer
    Molecular and cellular biochemistry 141 (1994), S. 9-13 
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    ISSN: 1573-4919
    Keywords: hepatocytes ; hypertension ; age ; desaturase ; essential fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract This study points out the hepatocyte interconversion of the linoleic acid family during hypertension. Hepatocyte Δ6 desaturase activity was higher in 1 month-old spontaneously hypertensive rats than in normotensive controls. A similar tendency was observed in 6 month-old SHR. Δ5 desaturase activity was higher only in 1 month-old spontaneously hypertensive rats as compared to controls. Desaturase activities were particularly high at the age of 6 months. The hepatocyte fatty acid composition showed an impairment of n-6 polyunsaturated fatty acid metabolism in spontaneously hypertensive animals. Changes were greater in the young prehypertensive rats than in adults. A storage of n-3 long chain fatty acids is remarkable in adult hypertensive rats, suggesting an alteration in peroxisomal oxidation. Such modifications may be related to the prostaglandin precursors availability to peripheral tissues such as kidney.
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    Effects of amlodipine on renal haemodynamics in mild to moderate hypertensive patients (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 307-311 
    Details
    ISSN: 1432-1041
    Keywords: Calcium antagonists ; Amlodipine ; hypertension ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study the efficacy and safety of short-term amlodipine administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduced blood pressure induced by treatment was associated with maintenance of renal function. After a run-in period with placebo, 30 hypertensive patients without cardiac or renal diseases were randomly allocated to a double-blind 4 weeks controlled study with amlodipine 10 mg once a day (15 patients) or placebo (15 patients). Renal haemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, with methods described by Schlegel and Gates, respectively. In addition, effective renal blood flow [ERBF=ERPF/(1-Ht)], filtration fraction (FF=GFR/ERPF) ERPF) and renal vascular resistance (RVR=MBP×80/ERBF) were calculated. Plasma renin activity (PRA), serum aldosterone (ALD) and urinary excretion of sodium (NaU) were evaluated. At the end of amlodipine administration a significant decrease (P〈0.001) in SBP, DBP and MBP from baseline values was observed. A significant decrease (P〈0.01) in RVR and significant increases (P〈0.05) in ERPF, ERBF and in NaU were also found, without relevant changes in GFR, FF, PRA and ALD. No significant variation in clinical and renal measurements was observed in the placebo group. No relevant side effects were observed in either group. In conclusion, amlodipine was effective in lowering blood pressure in mild to moderate hypertension and exerted favourable effects on renal haemodynamics and function.
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    Blood pressure monitoring: a chronobiological approach to hypertension diagnosis (1993)
    Springer
    Bulletin of experimental biology and medicine 115 (1993), S. 205-208 
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    ISSN: 1573-8221
    Keywords: hypertension ; monitoring ; chronobiological studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00847197
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    Na+ and K+ permeability of erythrocyte membranes and their phospholipid composition in patients with essential hypertension (1993)
    Springer
    Bulletin of experimental biology and medicine 115 (1993), S. 126-128 
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    ISSN: 1573-8221
    Keywords: hypertension ; erythrocyte permeability ; phospholipids ; total phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00847169
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    Synchronization and desynchronization of the “Hypertensive” heart (1993)
    Springer
    Bulletin of experimental biology and medicine 116 (1993), S. 778-780 
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    ISSN: 1573-8221
    Keywords: heart ; hypertension ; correlation analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00786148
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    Regulation of sodium and body fluid homeostasis during development: Implications for the pathogenesis of hypertension (1992)
    Springer
    Cellular and molecular life sciences 48 (1992), S. 345-351 
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    ISSN: 1420-9071
    Keywords: Renin-angiotensin ; development ; hypertension ; SHR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.
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    Effects of mental and physical stress on plasma catecholamine levels before and afterβ-adrenoceptor blocker treatment (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 11-15 
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    ISSN: 1432-1041
    Keywords: Stress ; Atenolol ; Bopindolol ; catecholamines ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a study in mild hypertensives, the impact of mental and physical stress on plasma epinephrine (E), norepinephrine (NE), and on their ratio (NE/E) was evaluated. The effect of twoβ-adrenoceptor blocking drugs, atenolol and bopindolol, on plasma catecholamine levels was also examined. Each stressful stimulus significantly increased the NE and E levels compared to rest. The increase was progressive from mental stress, through the handgrip test to the treadmill test. A slight decrease in the NE/E ratio was observed following mental stress and the handgrip test, while this ratio increased during the treadmill test. No significant impact of beta blocking treatment on catecholamine levels was observed under any test condition.
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    Isradipine improves platelet function in hypertensives (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 43-46 
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    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; platelet function ; prostaglandin system ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and β-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1α were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.
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    Lipid and apolipoprotein levels during therapy with pinacidil combined with hydrochlorothiazide (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 65-70 
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    ISSN: 1432-1041
    Keywords: Lipids ; Pinacidil ; Hydrochlorothiazide ; hypertension ; triglyceride ; cholesterol ; apolipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study determined the effect of pinacidil on the concentration of plasma lipids and apolipoproteins in male patients previously equilibrated with 25 mg hydrochlorothiazide twice daily. Pinacidil therapy given to 52 hypertensives at 25 to 100 mg daily for 8 weeks resulted in a reduction of systolic and diastolic blood pressure concurrently to reductions in plasma cholesterol and triglycerides with no change in low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). There was an associated decrease in apolipoproteins (Apo)B, C-III and E and elevation in ApoA-I. A parallel placebo group of 44 patients experienced reduction in diastolic blood pressure and an elevation in ApoA-I. These changes indicate that pinacidil will be a useful antihypertensive agent having properties on lipoprotein metabolism which would favor decreased risks of atherosclerosis.
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    URL: http://dx.doi.org/10.1007/BF00314922
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    Hair analysis for detection of beta-blockers in hypertensive patients (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 351-352 
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    ISSN: 1432-1041
    Keywords: Hair ; β-adrenoceptorblockers ; drug monitoring ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266365
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    A comparison of the effect of lisinopril and hydrochlorothiazide on electrolyte balance in essential hypertension (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 487-490 
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    ISSN: 1432-1041
    Keywords: Lisinopril ; Hydrochlorothiazide ; hypertension ; electrolyte balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of lisinopril 10–20 mg or hydrochlorothiazide 25–50 mg (each given once daily) on blood pressure, serum sodium, potassium and magnesium concentrations, total body potassium and urinary cation excretion were compared in a group of hypertensive patients using a double blind randomised crossover design. Each active treatment phase lasted six weeks and a total of sixteen patients completed the study. Both lisinopril and hydrochlorothiazide produced clinically significant decreases in blood pressure. However, lisinopril treatment produced a mean reduction of 14 mm Hg in sitting diastolic pressure compared with a 7 mm Hg reduction for hydrochlorothiazide treatment. This difference was statistically significant. The decrease in the concentration of serum potassium during hydrochlorothiazide treatment was greater than that during lisinopril treatment (0.53 vs 0.01 mmol·l−1). The absolute value of serum potassium was significantly lower on hydrochlorothiazide than on lisinopril therapy. Neither treatment had an effect on serum magnesium concentrations, nor was there any significant effect of either treatment on urine volume or urinary excretion of sodium, potassium or magnesium. There was a trend towards increased total body potassium concentration on lisinopril compared with a decrease in total body potassium on hydrochlorothiazide. However, this difference was just outside the range of statistical significance. Both treatments were equally well tolerated. The results indicate slight superiority of lisinopril over hydrochlorothiazide with regard to control of diastolic blood pressure with a better effect on overall electrolyte balance.
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    URL: http://dx.doi.org/10.1007/BF00314855
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  • 39
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    Increased platelet sodium-proton exchange rates in insulin-dependent (type 1) diabetic patients with nephropathy and hypertension (1992)
    Springer
    Molecular and cellular biochemistry 109 (1992), S. 167-172 
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    ISSN: 1573-4919
    Keywords: Na+/H+ exchanger ; diabetic nephropathy ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract In order to assess the potential role of the plasma membrane sodium-proton (Na−/H+) exchanger in the pathogenesis of diabetic nephropathy, we investigated 32 insulin dependent (type 1) diabetic patients and 21 control subjects. We tested the Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of platelets suspended in sodium propionate. Patients with diabetic nephropathy had significantly increased rates of Na+/H+ exchange (0.31 ± 0.06 s−1 × 10−2) when compared to those without nephropathy (0.24 ± 0.07, p 〈 0.05) or to a control group (0.23 ± 05, p 〈 0.05). Nine patients who were classified as hypertensive had a highly significant increase in the Na+/H+ exchange rates when compared to 23 non-hypertensive diabetic patients: 0.33 ± 0.04 versus 0.24 ± 0.06 (p 〈 0.001). There was no significant correlation between the Na+/H+ exchange rates and age, diabetes duration, glycated hemoglobin or fructosamine levels on the day of the test. In summary, the data presented here demonstrate an increase in the Na+/H+ exchange rate in insulin-dependent diabetic patients with nephropathy and hypertension
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  • 40
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    Insulin resistance and hypertension (1992)
    Springer
    Molecular and cellular biochemistry 109 (1992), S. 119-125 
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    ISSN: 1573-4919
    Keywords: insulin resistance/hyperinsulinernia ; hypertension ; captopril ; glucose transport ; erythrocytes ; adipocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229765
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  • 41
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    Lipid peroxidation in the aorta of normotensive and spontaneously hypertensive diabetic rats (1992)
    Springer
    Bulletin of experimental biology and medicine 113 (1992), S. 666-668 
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    ISSN: 1573-8221
    Keywords: lipid peroxidation ; aorta ; rats ; hypertension ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00783752
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  • 42
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    The circadian heart rate but not blood pressure profile is influenced by the timing of β-blocker administration in hypertensives (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 435-436 
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    ISSN: 1432-1041
    Keywords: Atenolol ; hypertension ; ß-adrenoceptor blockade ; blood pressure ; heart rate ; ambulatory ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265862
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  • 43
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    Effect of nifedipine on glucose potentiation of the acute insulin response to arginine in non-insulin-dependent diabetics (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 411-415 
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    ISSN: 1432-1041
    Keywords: Insulin secretion ; Nifedipine ; non insulin-dependent-diabetes mellitus- ; hyperglycaemia ; plasma insulin ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic β-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg·dl−1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P〈0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM.
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  • 44
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    Long-term haemodynamic effects of sustained-release trimazosin at rest and during exercise in essential hypertension (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 131-134 
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    ISSN: 1432-1041
    Keywords: trimazosin ; hypertension ; alpha1-adrenoceptor blocker ; essential ; exercise ; extracellular fluid volume ; haemodynamics ; plasma volume ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The long-term haemodynamic effect of sustained-release trimazosin (mean daily dose 418 mg) at rest and during exercise has been examined in 14 male patients (age 30–61 y) with previously untreated mild or moderate essential hypertension. Cardiac output (dye dilution), heart rate and intra-arterial blood pressure were measured supine and sitting at rest, and during bicycle exercise. After 11 months of trimazosin treatment the mean casual blood pressure was reduced from 165/106 mm Hg to 147/92 mm Hg. The intra-arterial systolic and diastolic pressure was reduced by 3–7% at rest and during 50, 100 and 150 W exercise. Total peripheral resistance was reduced by 8–14% and cardiac output was slightly higher (2–8%) in all situations. Stroke volume and heart rate remained unchanged, as did body fluid volumes (isotope dilution) and body weight. Side effects were minor and transient. Thus, the haemodynamic responses to trimazosin are similar to but weaker than those of other alpha1-adrenoceptor blockers. The efficacy of the sustained-release formulation of trimazosin was low and daily doses above 600 mg are likely to be needed by many patients.
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    URL: http://dx.doi.org/10.1007/BF00280066
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  • 45
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    Effects of doxazosin and atenolol on the fibrinolytic system in patients with hypertension and elevated serum cholesterol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 321-326 
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    ISSN: 1432-1041
    Keywords: Fibrinolysis ; hypertension ; atenolol ; doxazosin ; tissue plasminogen activator ; plasminogen activator inhibitor ; cholesterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Disturbances in the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the fibrinolytic system have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the fibrinolytic system in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.
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    URL: http://dx.doi.org/10.1007/BF00265838
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  • 46
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    Effects of captopril on diabetic nephropathy in hypertensive women (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 405-409 
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    ISSN: 1432-1041
    Keywords: Captopril ; Diabetes ; nephropathy ; hypertension ; glucose tolerance ; plasma lipids ; blood pressure ; long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of the angiotensin converting enzyme inhibitor captopril on blood pressure, proteinuria, creatinine clearance and metabolic control in diabetic nephropathy have been evaluated. Captopril 144 mg per day was given to 8 longstanding, insulin-dependent, diabetic females with nephropathy. The blood pressure was significantly reduced (systolic 45.4, diastolic pressure 30.6 and mean arterial pressure 33.8 mm Hg after 24 weeks of treatment). Plasma renin activity rose significantly from a basal value of 1.60 to 6.71 ng·ml−1·h−1, and so did serum potassium (from 4.57 to 4.83 mEq·l−1). Serum aldosterone fell from 161 to 70.9 pgm·ml−1 and from 27.3 to 15.3 μg·24 h−1 in plasma and urine, respectively, after 6 months on captopril therapy. Urinary protein excretion was decreased by about 48% and creatinine clearance remained unchanged throughout the study. Plasma triglycerides and cholesterol also remained unchanged, and glycosylated haemoglobin was significantly reduced from 13.8 to 10.2% after captopril. The results suggest that captopril is a useful drug to treat hypertension in patients suffering from diabetic nephropathy, as the decline in kidney function can be reduced without impairing glucose tolerance or the lipid profile.
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  • 47
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    Cadralazine versus prazosin as second-step treatment in hypertensive patients on beta-blockers: a randomized multicentre study (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 461-465 
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    ISSN: 1432-1041
    Keywords: Cadralazine ; hypertension ; prazosin ; metoprolol ; combined therapy ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) ≥ 95 mm Hg whilst on a beta-adrenoceptor-blocker. The doses of the beta-adrenoceptor-blocker (metoprolol SR 200 mg once daily) and cadralazine (10 mg once daily) were held constant during the study, while prazosin was individually titrated from 0.5 mg to a maximum of 2 mg tds. 108 patients (50 m and 58 f; mean age 54 y) were enrolled in 12 centres. Twelve patients withdrew due to adverse effects or poor efficacy (5 patients on prazosin and 7 on cadralazine). Both treatments induced a similar significant reduction in systolic blood pressure (SBP) and DBP, allowing normalization of BP in 58% of subjects on cadralazine and 55% on prazosin. Heart Rate (hR) increased significantly from 67 to 72 beats · min−1 in those on cadralazine and from 65 to 69 beats · min−1 on prazosin. Body weight was unchanged. Adverse effects were mild and typical of vasodilators, such as headache, flushing and dizziness. Physician evaluation of drug efficacy was not different between drugs, and cadralazine was rated better in terms of tolerability. Thus, in this multicentre study, cadralazine in the fixed dose of 10 mg once daily, as a second-step antihypertensive treatment in patients not satisfactorily controlled by a beta-adrenoceptor-blocker, was as effective and showed a similar side effect profile to prazosin given three times daily.
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    URL: http://dx.doi.org/10.1007/BF00315223
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  • 48
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    Impact of dilevalol on haemodynamic changes during emotional stress (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 67-70 
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    ISSN: 1432-1041
    Keywords: Dilevalol ; oxprenolol ; hypertension ; emotional stress ; haemodynamic changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single dose of 200 mg dilevalol, β-adrenoceptor blocker with additional vasodilating properties, and 200 mg oxprenolol on haemodynamic changes induced by emotional stress have been compared in 12 male young Caucasian patients with newly diagnosed labile hypertension. No difference was noted in the stress-induced increase of total peripheral resistance (TPR) following administration of the two substances (11% versus 6%). However, dilevalol revealed a vasodilating action by decreasing TPR at rest (from 1004 to 951 dyn·s·cm−5) and diastolic blood pressure (BP) (from 87 to 75 mm Hg) whereas TPR at rest remained unchanged after the intake of oxprenolol.
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    URL: http://dx.doi.org/10.1007/BF00315141
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  • 49
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    Effects of diltiazem and metoprolol on blood pressure, adverse symptoms and general well-being (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 453-460 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; metoprolol ; quality of life ; hypertension ; multicentre study ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary General well-being, adverse effects and antihypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120–240–360 mg/day or metoprolol 50–100–200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mm Hg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mm Hg (SBP/DBP). Target pressures (DBP ≤ 90 mm Hg and/or a reduction in DBP of ≥ 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose-dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120–360 mg and 50–200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being.
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    Angiotensin converting enzyme inhibition in Dahl salt-sensitive rats (1991)
    Springer
    Molecular and cellular biochemistry 104 (1991), S. 45-50 
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    ISSN: 1573-4919
    Keywords: hypertension ; Dahl rats ; angiotensin converting enzyme ; cardiac hypertrophy ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Angiotensin II has previously been reported to have in vivo and in vitro cardiac hypertrophic effects. We used the salt-sensitive Dahl rat genetic strain to separate mechanical (pressure overload) vs. hormonal (renin-angiotensin system) input in cardiac hypertrophy. Blood pressure was significantly increased and left ventricular hypertrophy, as indexed by LV/BW ratios, was present at 7 and 15 days in rats receiving 4% and 8% NaCl compared to the 1% controls. There was no effect of the angiotensin converting enzyme inhibitor, enalapril maleate, on lowering the blood pressure in 8% NaCl-treated animals, however, there was a significant reduction in LV/BW ratio in 8% NaCl-treated animals that received this drug. Left ventricular angiotensinogen mRNA activity was significantly reduced in rats receiving 4% and 8% NaCl. In this model of hypertension the cardiac hypertrophy which develops is largely dependent on mechanical forces though there remains a significant contribution to this process from either circulating or localized angiotensin II production. Regulation of angiotensinogen gene expression in the hypertrophied left ventricle suggests that volume and electrolyte control of angiotensinogen gene expression in the heart and/or hereditary factors are predominant in the control of regulation of this gene in the left ventricle of Dahl rats.
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    URL: http://dx.doi.org/10.1007/BF00229802
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  • 51
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    Functional activity of the venous system during hypertension development in rats (1991)
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    Bulletin of experimental biology and medicine 111 (1991), S. 598-602 
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    ISSN: 1573-8221
    Keywords: electric field of the heart ; portal vein ; smooth muscle cells ; hypertension ; spontaneously hypertensive rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00840992
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  • 52
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    Co-dergocrine mesylate inhibits the increase in plasma catecholamines caused by nifedipine in essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 435-439 
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    ISSN: 1432-1041
    Keywords: co-dergocrine mesylate ; hypertension ; aldosterone ; catecholamines ; nifedipine ; renin side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure 〉 105 mm Hg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment. Blood pressure was significantly lower (P 〈 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg · ml−1 and in epinephrine from 67 to 55 pg · ml−1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg · ml−1 with preceding Cod to 331 pg · ml−1 was much less than the increase with placebo as premedication, from 284 to 440 pg · ml−1. Nif caused an increase in renin activity but no increase in aldosterone. Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication. Due to the stabilizing action of Cod on catecholamines and on the side effects of Nif, Cod may be preferable to other antihypertensives in augmenting the antihypertensive action of Nif.
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  • 53
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    Cardiac arrhythmias as correlated with the circadian rhythm of arterial pressure in hypertensive subjects with and without left ventricular hypertrophy (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. S49 
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    ISSN: 1432-1041
    Keywords: arrhythmia ; hypertension ; LVH ; holter monitoring ; BP monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the relationship among supraventricular and ventricular arrhythmias with blood pressure and heart rate (HR) values, we studied 2 groups of 20 hypertensive men with (group I) and without (group II) left ventricular hypertrophy. Ambulatory electrocardiographic tracings were recorded continuously, together with ambulatory arterial pressure. Systolic (SBP) and diastolic (DBP) blood pressure values measured over 24 h showed no difference between the two groups, but we found greater variability in SBP in group I. The incidence of ventricular and supraventricular arrhythmias was significantly higher in patients of group I; moreover, we found a strong correlation between the incidence of ventricular extrasystoles (VPCs) and SBP, DBP, and HR values in group I, whereas in group 11 the incidence of supraventricular extrasystoles (APCs) was higher during peaks of SBP and HR values. The relationship between APCs and SBP observed in group II may be attributable to the pressure stimulus on a normal atrium, and the significant correlation between VPCs and SBP, DBP, and HR values may be due to episodes of subendocardial ischemia or to the influence of adrenergic stimulation on previously compromised myocardial tissue.
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    The pharmokinetics of isradipine in hypertensive subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 209-211 
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    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; pharmacokinetics ; pharmacodynamics ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In conjunction with a multicentre clinical trial of the calcium antagonist isradipine in hypertension, pharmacokinetic and pharmacodynamic studies were conducted in 9 subjects. An initial dose of 5 mg (capsule formulation) of isradipine was given orally. The mean Cmax, tmax and AUC(0–8) were 6.0 ng · ml−1, 1.5 h and 15.1 h · ng · ml−1 respectively. Seven subjects repeated the study at steady state after 10 week's dose titration with isradipine. Cmax, tmax and AUC(0–8) were 3.7 ng · ml−1, 1.2 h and 12.2 h · ng · ml−1 respectively indicating that the drug does not accumulate over time. Control of blood pressure paralleled plasma isradipine concentrations which suggested that the drug should be given at least twice daily. Pharmacokinetic studies performed in conjunction with clinical trials can provide valuable information about the patterns of drug response.
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  • 55
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    Effects of carvedilol on serum lipids in hypertensive and normotensive subjects (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S139 
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    ISSN: 1432-1041
    Keywords: carvedilol ; serum lipid metabolism ; hypertension ; normotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of carvedilol (an α · β-blocker) on lipid metabolism were assessed in addition to its hypotensive effect. The subjects were 18 men and 18 women, 20 with hypertension and 16 normotensives with other conditions requiring carvedilol treatment. They were aged from 31 to 79 years and were given a daily dose of 5–20 mg carvedilol (average, 9.7 mg/day) for 12 weeks. Significant falls were seen in blood pressure and heart rate after 12 weeks in the hypertensive subjects (mean ± SE) (systolic: from 164 ± 2 to 141 ± 2 mm Hg,P 〈 0.001; diastolic: from 98 ± 1 to 85 ± 2 mm Hg,P 〈 0.001; heart rate: from 71 to 65 beats/min,P 〈 0.001). Smaller changes in blood pressure and heart rate were seen in the normotensive subjects, with the fall in systolic pressure being significant (from 143±3 to 135 ± 2 mm Hg,P 〈 0.01). There were no significant changes in the overall serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and phospholipid levels. In the subgroup with a pretreatment serum triglyceride level of 〉 150 mg/dl, a significant fall of 52.1 mg/dl was seen (P 〈 0.05). Lipoprotein analysis showed a significant fall in α-lipoprotein levels (P 〈 0.05). The atherogenic index did not change significantly, and it was concluded that carvedilol was an effective antihypertensive agent that produced no adverse effects and possibly had beneficial effects on lipid metabolism.
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    Efficacy and safety of carvedilol in comparison with atenolol in hypertensive patients pretreated with hydrochlorothiazide (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S147 
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    ISSN: 1432-1041
    Keywords: hypertension ; combination treatment ; hydrochlorothiazide ; carvedilol ; atenolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carvedilol [25 mg once daily] (o. d.) was compared to atenolol (50 mg o. d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP),100–115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o. d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group,n = 54; A/HCTZ group,n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of 〈 90 mmHg. In a relatively low number of patients (6 of 131), a response as defined above was achieved with HCTZ alone. This may be accounted for by the fact that patients were required to have a diastolic blood pressure of at least 100 mgHg and by the relatively short period of monotherapy. The two groups of patients receiving different combination treatments were well matched for demographic data and blood pressure values before the adjunct was added. In both groups there was a marked additional blood pressure decrease on the initiation of combined treatment. At the end of the study the medians of all blood pressure values were well within normal ranges, which was not the case with HCTZ alone. On the last day of the trial, the responders comprised 67% of the C/HCTZ group and 71% of the A/HCTZ group. No relevant changes in lipid values were observed with combination treatment vs diuretic monotherapy. No serious adverse event attributable to one of the study drugs was reported. The results of the present trial suggest that the antihypertensive efficacy of both combinations is superior to that of HCTZ alone and that there is no difference in efficacy between the two combinations. Adding carvedilol or atenolol to pre-existing HCTZ appears to be safe. The tolerability of the antihypertensive treatment does not seem to decline, despite considerable additional decreases in blood pressure.
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    Verapamil in antihypertensive treatment of patients on renal replacement therapy — clinical implications and pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. S35 
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    ISSN: 1432-1041
    Keywords: Verapamil ; renal replacement therapy ; hypertension ; pharmakokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-eight hypertensive patients on renal replacement therapy (HD, HF, PD) were treated with verapamil (Isoptin RR-slow release) in an open label study. Blood pressure was satisfactorily reduced in 21 patients (84%). Due to adverse reactions the treatment had to be discontinued in 4 patients. Verapamil clearances were calculated according to different dialysis methods. No changes in dose or mode of application of verapamil were necessary using any mode of renal replacement therapy.
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    URL: http://dx.doi.org/10.1007/BF01409205
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    Age-related antihypertensive and haemodynamic effects of verapamil SR: Clinical results and effects on atrial natriuretic peptide (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. S29 
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    ISSN: 1432-1041
    Keywords: hypertension ; verapamil haemodynamics ; atrial natriuretic peptide ; elderly ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of the calcium-antagonist verapamil was investigated in two groups of patients, adult hypertensives (AH, 〈 65 years of age) and elderly hypertensives (EH, 〉 65 years of age), who were treated with 240 mg p. o. sustained-release (SR) verapamil for 4 months. Arterial blood pressure was significantly reduced in both groups: the responders' rate was 65% in the AH group and 82% in the EG group. The heart rate was slightly but not significantly reduced. An improvement in cardiac haemodynamics was observed [cardiac index (CI), from 3.00 ± 0.51 to 3.25 ± 0.83 ml min−1 m−2 in AH and from 2.35 ± 1.08 to 3.04 ± 0.86 ml min−1 m−2 in EG]. We also evaluated the plasma concentrations of atrial natriuretic peptide (ANP) before and after treatment; ANP levels increased significantly only in the EH group. No serious side effects occurred. In conclusion, verapamil SR provided effective and well-tolerated antihypertensive treatment in both adult and elderly patients.
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    The haemodynamic effects of long term felodipine therapy in previously untreated essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 539-543 
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    ISSN: 1432-1041
    Keywords: Felodipine ; hypertension ; vasodilator ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of 〈 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm−5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure.
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    A comparison of the acute effects of cicletanine and bendrofluazide on urinary electrolytes and plasma potassium in essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 227-232 
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    ISSN: 1432-1041
    Keywords: cicletanine ; bendrofluazide ; hypertension ; urinary electrolytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects. In view of evidence that with long-term treatment both cicletanine 50 and 100 mg have anti-hypertensive effects, these findings suggest that cicletanine may act by a different mechanism in lowering blood pressure at low and high dose.
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    Effect of diuretics on captopril-induced urinary zinc excretion (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 359-361 
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    ISSN: 1432-1041
    Keywords: urinary zinc ; captopril ; furosemide ; hydrochlorothiazide ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary zinc/creatinine ratio has been measured in five groups of patients with essential hypertension and in a group of healthy controls. The first four groups of patients consisted of subjects being treated for at least three months with captopril alone, hydrochlorothiazide alone, captopril plus hydrochlorothiazide, or captopril and furosemide. The fifth group comprised hypertensive patients not on any medication. The first four patient groups exhibited significantly increased urinary zinc/creatinine ratios when compared to the control and untreated hypertensive groups, but in the two combination regimens there was little zincuria. It is suggested that both diuretics inactivate the zincuric effect of captopril by binding to its sulphhydryl group within the tubular lumen.
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    Do different hemodynamic effects of antihypertensive drugs translate into different safety profiles? (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S134 
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    ISSN: 1432-1041
    Keywords: hypertension ; physiologic effects ; diuretics ; vasodilators ; beta-blockers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various antihypertensive drugs reduce blood pressure by different mechanisms. In some instances, adverse reactions occur because of specific hemodynamic effects. Examples include syncope with alpha-blockade or vasodilator therapy; fatigue or exercise intolerance with the reduction in cardiac output following the use of beta-adrenergic inhibitors; edema, headaches, or dizziness with the use of vasodilators such as calcium entry blockers; renal failure in patients with renal artery stenosis or renal insufficiency following the use of ACE inhibitors; and marked hyponatremia with volume depletion following the use of diuretics, especially in elderly patients. In the majority of patients, however, blood pressure lowering can be achieved without significant adverse effects. Combining small doses of different agents with different hemodynamic actions often results in good blood pressure control and minimal reactions. Examples of these include diuretics and beta-adrenergic inhibitors, diuretics and ACE inhibitors, and beta-blockers and vasodilators.
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    The use of carvedilol in elderly hypertensive patients (1990)
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    European journal of clinical pharmacology 38 (1990), S. S129 
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    ISSN: 1432-1041
    Keywords: carvedilol ; metoprolol ; pindolol ; nitrendipine ; hypertension ; vasodilator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carvedilol, a β-blocking drug with vasodilator activity, has been used in 4 studies in 107 elderly patients with essential hypertension and has reduced blood pressure effectively. In the first study the pharmacokinetics and clinical response were compared between 21 patients 〉 65 years of age and 8 patients aged 35–50 years). The peak blood levels, time to maximal concentration, area under the curve, half-life and trough level of the drug with chronic administration did not differ. The clinical responses to the drug were similar, with a greater fall in systolic blood pressure in the older group. However the initial systolic blood pressure in the older group was higher. Carvedilol was compared with metoprolol, pindolol and nitrendipine in elderly patients. The responses to carvedilol were at least equal to those obtained with the other drugs. Control was achieved in the three studies with once-daily therapy. There was no significant postural hypotensive effect. A feature of all studies was the large number of patients who responded to carvedilol. The side-effect profile of the drug was acceptable; headache and dizziness were more common than with placebo or the comparison drugs and were frequently associated. There were no adverse biochemical effects and the lipid profile was not altered. Carvedilol is an effective antihypertensive drug that lowers blood pressure equally well in the young and the old.
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    Acute haemodynamic and neurohumoral effects of intravenous nisoldipine in patients with severe congestive heart failure (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 11-15 
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    ISSN: 1432-1041
    Keywords: nisoldipine congestive heart failure ; haemodynamic effect blood pressure plasma renin activity ; plasma norepinephrine ; hypertension ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continous infusion of 0.2 μg · kg−1 · min−1. Haemodynamic measurements were performed at baseline and after 30 min. The mean arterial pressure fell from 91 to 73 mm Hg, pulmonary capillary wedge pressure from 31 to 26 mm Hg and systemic vascular resistance from 1695 to 1040 dyn · s · cm−5. The cardiac index (2.2 to 2.71 · min−1 · m−2, and stroke volume index (25 to 33 ml · m−2) were markedly increased. There was no reflex tachycardia as the heart rate dropped from 92 to 85 beats · min−1. Plasma renin activity and norepinephrine concentration did not change significantly. The findings indicate that nisoldipine acts as a strong vasodilator and that it has a beneficial acute haemodynamic effect in patients with severe left heart failure irrespective of its aetiology.
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    Renal effects of nicardipine, a calcium antagonist, in hypertensive type 2 (non-insulin-dependent) diabetic patients with and without nephropathy (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 425-429 
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    ISSN: 1432-1041
    Keywords: nicardipine ; diabetic nephropathy ; calcium antagonist ; hypertension ; renal function ; albuminuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal effects of oral maintenance doses of nicardipine 60–120 mg/day have been studied in 18 hypertensive patients with Type 2 (non-insulin-dependent) diabetes mellitus: 6 with normoalbuminuria (urinary albumin excretion rate, AER 〈20 μg · min−1, Group A); 6 with incipient nephropathy, (AER 20–200 μg · min−1, Group B); and 6 with overt nephropathy (AER 〉200 μg · min−1, Group C). Treatment for 4 weeks significantly lowered the systolic and diastolic blood pressures and reduced total renal vascular resistance in all three groups. Nicardipine increased renal blood flow significantly in Group C and slightly in Group B, and had no effect in Group A. Glomerular filtration rate remained unchanged in all three groups. It significantly reduced AER and the fractional clearance of albumin in Group B, whereas AER in Groups A and C was not altered. Plasma renin activity, aldosterone concentration, osmotic pressure, serum total protein and albumin concentrations and haemoglobin A1c level were similar in the control and nicardipine phases in all three groups. The results suggest that nicardipine may preserve renal function whilst having a concomitant hypotensive action in hypertensive Type 2 diabetic patients with normoalbuminuria and incipient nephropathy, and that the drug may improve renal blood flow in patients with overt nephropathy. The effect of the drug on urinary albumin excretion may deserve further investigation.
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    Effect of nifedipine monotherapy on platelet aggregation in patients with untreated essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 403-404 
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    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; lipids ; platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of 6 weeks of nifedipine 30–60 mg/d on platelet aggregation and lipid parameters has been studied. A diminution in ADP-, adrenaline- and collagen-induced aggregation was observed. In the case of adrenaline-and collagen-stimulated aggregation the decrease was statistically significant. It was found that platelets which aggregated markedly during the placebo treatment were most strongly inhibited by nifedipine. The changes in lipid parameters were not significantly correlated with changes in aggregation.
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    Dose adjustment of nifedipine in hypertensive patients (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 17-20 
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    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; concentration-effect relationship ; individual dose ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with essential hypertension (WHO grade I–II) were treated in an open dose-adjustment study with the standard regimen of slow-release nifedipine 20 mg b. d. for 2 weeks and with an individualized dose for 6 weeks. The optimum dose, defined as that producing a pre-dose diastolic blood pressure (dBP) of 90 mm Hg at steady state, was determined from the individual concentration-effect relationship after a test-dose of 20 mg. On standard therapy, the reduction in pre-dose dBP was inadequate in 4 patients and it was excessive in 1 patient. After 2 weeks of individualized treatment, the required pre-dose antihypertensive effect was obtained in all patients. The individual doses required were 10 mg b. d., 10 mg t. d. s. 20 mg b. d., 20 mg t. d. s. and 20 mg q. d. s. One patient dropped out of the study because of side effects. Loss of the antihypertensive effect was observed in one patient after 6 weeks of treatment. On the optimized dose, the average value of the pre-and 2 h post-dose steady state nifedipine concentrations (27.6 μg/l) compared well with model-derived optimum concentrations (28.6 μl/l) (r=0.9210). The results show that the dose of nifedipine can be accurately predicted using the individual concentration-effect relationship after a single dose.
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    A randomized double-blind study of bisoprolol versus atenolol in mild to moderate essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: bisoprolol ; atenolol ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have compared the efficacy and pharmacokinetics of bisoprolol, a new cardioselective beta-adrenoceptor antagonist, with atenolol in a randomized double-blind crossover study in 12 patients (mean age 53.5 y) with mild to moderate essential hypertension. After a two week placebo wash-out period without any antihypertensive therapy, the patients were given bisoprolol 10 mg daily or atenolol 50 mg daily, increasing to 20 mg or 100 mg respectively if the sitting diastolic blood pressure did not fall below 90 mm Hg after two weeks of therapy. Crossover occurred after six weeks of active therapy followed by two weeks of placebo wash-out. After 6 weeks of therapy both drugs significantly reduced sitting and standing diastolic blood pressures (bisoprolol by 15% and 16% respectively, atenolo by 11% in both cases). However, while sitting and standing systolic pressures were significantly reduced by bisoprolol (13% and 16% respectively), only standing systolic pressures were significantly reduced by atenolol (11%), and this reduction was significantly less than with bisoprolol (p〈0.05). Both drugs similarly reduced mean sitting and standing heart rates. There were no significant differences between the single-dose and steady-state kinetics of either bisoprolol or atenolol. The mean plasma elimination half-life (t1/2) increased from 12.9 to 13.2 h during steady state on bisoprolol and from 7.2 to 11.5 h on atenolol. The apparent volume of distribution (Vz) was greater for bisoprolol than for atenolol after single dosing (235 1 vs 146 1) and at steady state (216 1 vs 137 1), but clearances were similar for both drugs. The maximum plasma concentration (Cmax) of bisoprolol increased from 45 μg·l−1 to 72 μg·l−1 during steady state and the Cmax of atenolol increased from 321 μg·l−1 to 410 μg·l−1 Adverse effects occurred in only one patient (lethargy while taking atenolol). These results suggest that bisoprolol has similar efficacy, safety, and pharmacokinetics to atenolol in patients with mild to moderate essential hypertension.
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    The influence of chronic treatment with verapamil on plasma atrial natriuretic peptide levels in young and elderly hypertensive patients (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. S39 
    Details
    ISSN: 1432-1041
    Keywords: ANP ; verapamil ; hypertension ; age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled crossover study, the plasma atrial natriuretic peptide (ANP) levels of nine young and ten elderly hypertensive patients were compared after placebo and after treatment with 120 mg verapamil given three times daily over 4 weeks. During placebo, plasma ANP levels proved to be higher in elderly patients than in young subjects. Chronic treatment with verapamil induced a rise in ANP levels in both young and elderly patients with hypertension.
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    Effect of furosemide on angiotensin II-mediated prostaglandin I2 production in hypertensive subjects (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 113-115 
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    ISSN: 1432-1041
    Keywords: Furosemide ; 6-keto-PGF1α ; hypertension ; angiotensin II ; captopril ; urinary PGs ; PGI2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of angiotensin II (AII) in Prostaglandin I2 (PGI2) production following furosemide has been examined in a placebo-controlled, cross-over study. Furosemide 20 mg was injected intravenously in eight hypertensive subjects already treated with oral captopril 25 mg or a matching placebo. Urinary excretion of 6-keto-PGF1α (a metabolite of PGI2) and PGE2, PRA and AII was increased following furosemide without captopril pretreatment. The rises in urinary 6-keto-PGF1α and PGE2, and plasma AII after furosemide were prevented by the captopril pretreatment. Urinary volume, sodium and furosemide were not affected by captopril. The data indicate that the effect of furosemide on PGI2 production, as reflected by the urinary excretion of 6-keto-PGF1α, was mediated by an action of AII.
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    Conversion of drug-induced SLE-syndrome by the vasodilating agent cadralazine (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 303-303 
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    ISSN: 1432-1041
    Keywords: cadralazin ; lupus erythematosus ; hydralazine ; SLE-syndrome ; case report ; hypertension ; adverse reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disappearance of a drug induced SLE syndrome in a 43 year old man, was described. He replaced antihypertensive agent hydralazine by an other vasodilatating agent cadralazine.
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    Comparison of the renal effects of dilevalol and carteolol in patients with mild to moderate essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 305-307 
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    ISSN: 1432-1041
    Keywords: dilevalol ; carteolol ; hypertension ; vasodilator properties ; β-blocker ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of 6 weeks of treatment with dilevalol 100 mg once daily, or carteolol 10 mg once daily, on renal blood flow (RBF), glomerular filtration rate (GFR) and total renal vascular resistance (TRR) were studied in 10 patients with mild-to-moderate essential hypertension in a randomised cross-over experiment. Both drugs lowered the systolic and diastolic blood pressures to a similar extent without altering the heart rate. Carteolol non-significantly decreased RBF by 9.2% and GFR by 12.3% without altering. TRR, whereas dilevalol produced a significant reduction in TRR by 13.2% (p〈0.05), a non-significant decrease in RBF by 4.6% and no change in GFR. Neither drug changed plasma osmotic pressure, serum total protein concentration, electrolytes or plasma aldosterone concentration. Plasma renin activity tended to be lower in the dilevalol phase as compared to the carteolol phase. The results suggest that dilevalol may cause a greater decrease in TRR and less reduction in GFR when compared to carteolol in patients with mild-to-moderate essential hypertension. The difference in the renal effects might be due to the difference in the potency of vasodilatory properties of both drugs at the doses applied.
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    The role of multiple action agents in hypertension (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S89 
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    ISSN: 1432-1041
    Keywords: hypertension ; hemodynamics ; alpha-blokkers ; beta-blockers ; multiple-action agents ; labetalol ; dilevalol ; carvedilol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A 20-year follow-up study of central hemodynamics in essential hypertension at rest and during exercise in 61 men with uncomplicated essential hypertension has clerarly shown that hemodynamic disturbances depend on the age of the subjects and the severity of the hypertensive state and that a shift in the hemodynamic alterations take place overtime. During 10- and 20-year follow-up, central hemodynamics changed towards a low cardiac-index (CI) — high total peripheral-resistance index (TPRI) pattern. With increasing age there was a gradual reduction in CI as well as stroke index (SI). The arteriovenous oxygen difference increased, particularly during exercise. The 20-year treatment with conventional drugs (beta-blockers and/or diuretics) did not prevent a marked increase in TPRI and a marked reduction in CI and SI in subjects initially 40–49 years of age. In recent years, beta-blockers with vasodilating activity have been introduced in the treatment of hypertension (labetalol, prizidilol, dilevalol and carvedilol). The hemodynamic effects of these compounds clearly differ from the changes induced during acute and chronic conventional beta-blocking treatment. In contrast to usual beta-blockers, these drugs reduce TPRI acutely and the reductions they produce in heart rate (HR) and CI are considerably lower. Our long-term data on labetalol (n =15), prizidilol (n =15) and dilevalol (n =17) indicate a persistent reduction in TPRI and litte or no decrease in exercise CI. Long-term data on carvedilol are not yet available. Approximately 70% of patients with mild to moderately severe essential hypertension achieved normal blood pressure during chronic treatment on beta-blockers with vasodilating activity.
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    Effects of carvedilol on cerebral blood flow and its autoregulation in previous stroke patients with hypertension (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. S120 
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    ISSN: 1432-1041
    Keywords: carvedilol ; cerebral blood flow ; CBF autoregulation ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied the effects of oral carvedilol (20 mg/day) on cerebral blood flow (CBF) and CBF autoregulation in ten previous stroke patients with hypertension. Measurement of CBF was done by the argon inhalation method. CBF autoregulation was also studied by the (A-V)O2 method after stepwise reduction in systemic blood pressure. After 1 week of carvedilol administration, the mean arterial blood pressure showed an 18% decrease, with no significant changes in CBF, CBF autoregulation, or other cerebral circulation parameters. From these findings, it can be said that carvedilol is a potent anti-hypertensive agent that does not affect cerebral circulation parameters.
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    URL: http://dx.doi.org/10.1007/BF01409479
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    Antihypertensive and renal effects of enalapril and slow-release verapamil in essential hypertension (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. S41 
    Details
    ISSN: 1432-1041
    Keywords: Enalapril ; hypertension ; renal function ; verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal, metabolic and antihypertensive effects of enalapril (E) and slow-release verapamil (V) were compared in a 2-month double-blind crossover trial in 22 patients with newly discovered essential hypertension. The glomerular filtration rate and renal vascular resistance were unaltered; renal blood flow was slightly decreased by V Serum Ca2+ increased and Na+ excretion declined after V. Serum lipids, glucose, and erythrocyte electrolytes were unchanged. Blood pressure (BP) was lower with E after half the maximum dosage compared with V but similar BP reductions were obtained after 2 months with the maximum dosage.
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    URL: http://dx.doi.org/10.1007/BF01409207
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    Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 299-300 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; atenolol ; hypertension ; blood pressure ; essential ; serum lipids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n=44) was compared with placebo and atenolol (n=43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315116
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    Collagen and the myocardium: fibrillar structure, biosynthesis and degradation in relation to hypertrophy and its regression (1990)
    Springer
    Molecular and cellular biochemistry 96 (1990), S. 1-14 
    Details
    ISSN: 1573-4919
    Keywords: type I and III collagen ; fibrosis ; hypertension ; collagen gene expression ; collagen degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The extracellular matrix of the myocardium contains an elaborate structural matrix composed mainly of fibrillar types I and III collagen. This matrix is responsible for the support and alignment of myocytes and capillaries. Because of its alignment, location, configuration and tensile strength, relative to cardiac myocytes, the collagen matrix represents a major determinant of myocardial stiffness. Cardiac fibroblasts, not myocytes, contain the mRNA for these fibrillar collagens. In the hypertrophic remodeling of the myocardium that accompanies arterial hypertension, a progressive structural and biochemical remodeling of the matrix follows enhanced collagen gene expression. The resultant significant accumulation of collagen in the interstitium and around intramyocardial coronary arteries, or interstitial and perivascular fibrosis, represents a pathologic remodeling of the myocardium that compromises this normally efficient pump. This report reviews the structural nature, biosynthesis and degradation of collagen in the normal and hypertrophied myocardium. It suggests that interstitial heart disease, or the disproportionate growth of the extracellular matrix relative to myocyte hypertrophy, is an entity that merits greater understanding, particularly the factors regulating types I and III collagen gene expression and their degradation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228448
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    Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 249-256 
    Details
    ISSN: 1432-1041
    Keywords: ramipril ; renal insufficiency ; hypertension ; pharmacokinetics ; ramiprilat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1–2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5–15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15–40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40–80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex. The study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min) smaller doses of ramipril are required than in patients with normal or borderline renal function.
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    URL: http://dx.doi.org/10.1007/BF00679779
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    Renal and hormonal effects of alpha1-adrenoceptor blockade by bunazosin in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 575-578 
    Details
    ISSN: 1432-1041
    Keywords: bunazosin ; hypertension ; alpha1-adrenoceptor blocker ; blood pressure ; renal blood flow ; renal function ; renin ; aldosterone ; atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal and hormonal effects of the α1-adrenoceptor blocker bunazosin were examined in 6 patients with essential hypertension. Oral bunazosin for 4 to 12 weeks significantly decreased mean blood pressure by 10%, increased effective renal blood flow and creatinine clearance by 34% and 37%, respectively, the plasma norepinephrine concentration was elevated by 60%, and the plasma atrial natriuretic peptide level was lowered by 22%. The plasma renin activity and aldosterone concentration were unchanged. Thus, a moderate reduction in blood pressure was produced by bunazosin treatment while maintaining renal perfusion.
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    URL: http://dx.doi.org/10.1007/BF00637738
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    Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 459-465 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
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    URL: http://dx.doi.org/10.1007/BF00558124
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    Enalapril and hydrochlorothiazide in hypertensive Africans (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 229-234 
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    ISSN: 1432-1041
    Keywords: enalapril ; hydrochlorothiazide ; hypertension ; side-effects ; Africans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy both of angiotensin converting enzyme (ACE) inhibitors and thiazide diuretics has been claimed to be influenced by plasma renin activity, which declines with age and is low in blacks. In a double-blind, placebo-controlled, double-dummy, randomized, parallel-group preliminary study, the antihypertensive efficacy and tolerability of the ACE inhibitor enalapril (20 mg day−1) and hydrochlorothiazide (50 mg day−1) were evaluated and compared for 4 weeks in 20 African patients with essential hypertension. The two groups had similar baseline clinical features and serum Na+ and K+ levels. Hydrochlorothiazide caused a significant and sustained fall in erect blood pressure with a reflex tachycardia. Enalapril exerted only a modest antihypertensive action, but significantly reduced erect heart rate. Direct comparison of hydrochlorothiazide — and enalapril — induced hypotension suggested a greater fall in subjects on the thiazide. The 95% confidence limits for the thiazide-enalapril difference in antihypertensive action at the end of the study was 39.5 to −7.5 mm Hg systolic and 22.0 to −6.6 mm Hg diastolic. The maximal blood pressure fall after hydrochlorothiazide was positively correlated with age (r=0.50;p〈0.05), whilst that of enalapril was inversely related age to (r=−0.57,p〈0.05). The results are compatible with the notion that ACE inhibitor monotherapy may be less effective than thiazide diuretic treatment in African and black patients with essential hypertension. The findings also support the concept that age and racial factors may influence the response to antihypertensive treatment.
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    URL: http://dx.doi.org/10.1007/BF00558152
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    Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 567-573 
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    ISSN: 1432-1041
    Keywords: isradipine ; hypertension ; blood pressure ; calcium entry blockade ; renin angiotensin system ; aldosterone plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng · kg−1 · min−1 was given before (control) and 30 min after the oral administration either of IS or P. After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II. In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.
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    URL: http://dx.doi.org/10.1007/BF00637737
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    Ambulatory blood pressure monitoring during sustained treatment with conventional and extended-release felodipine in mild-to-moderate hypertension (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 555-557 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; ambulatory blood pressure monitoring ; slow-release formulation ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the duration of the antihypertensive effect of the dihydropiridine calcium antagonist felodipine in conventional (C-F) and slow-release (ER-F) formulations, 12 patients with essential hypertension underwent ambulatory blood pressure monitoring (ABPM) at the end of a 2-week treatment period with C-F 5 mg b.d., ER-F 10 mg once daily (o.d.) and placebo. C-F, ER-F and placebo were given in a double-blind 3×3 latin square design 4 times replicated. There was no systematic change in the ABP profile over the three study periods regardless of the treatment. In comparison to placebo, the mean 24-h systolic and diastolic blood pressures showed a significant and similar reduction after both formulations of F. Compared to placebo, C-F and ER-F induced a significant reduction in systolic blood pressure for 15 and 21 h, respectively, and of diastolic blood pressure for 16 and 21 h, respectively. Three patients complained of headache (mild in 2, moderately severe in 1), and two patients of nocturia, with either formulation of F.
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    URL: http://dx.doi.org/10.1007/BF00562543
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    Effect of nicardipine on insulin secretion, glucose and lipid metabolism in hypertensive, non-insulin dependent diabetics (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 1-4 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; insulin ; glucose ; diabetes ; hypertension ; metabolic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v. GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl·90 min on placebo, 33.1 mg/dl·90 min acutely and 31.4 mg/dl·90 min on chronic administration of nicardipine; insulin 2.08 µU/ml·90 min on placebo, 1.87 µU/ml·90 min acutely and 1.93 µU/ml·90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v. GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%. min−1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.
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    URL: http://dx.doi.org/10.1007/BF00561014
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    Is captopril effective in controlling blood pressure when administered once daily? An assessment using 24-h ambulatory blood pressure monitoring (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 11-15 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; once-daily administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve patients with essential hypertension receiving captopril monotherapy or captopril in conjunction with a diuretic had their 24-h blood pressure profiles monitored using an automatic, non-invasive ambulatory method. The study examined the efficacy of once a day versus twice a day administration of the ACE inhibitor in controlling blood pressure. Six untreated subjects with borderline hypertension were also studied using the same monitoring equipment and with the same frequency, to act as controls because of the possibility of repeated use of the device causing a ‘familiarisation’ effect. The results obtained indicated that if anything, the once daily dosing produced marginally better blood pressure values. The amplitude of the diurnal blood pressure variation was reduced on a ‘second-wearing’ of the monitoring equipment suggesting some degree of familiarisation with the apparatus.
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    URL: http://dx.doi.org/10.1007/BF00561016
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    Effect of carteolol on renal function in healthy subjects and patients with hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 83-86 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; hypertension ; chronic renal failure ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of short- and long-term administration of carteolol on renal function has been examined in healthy subjects and in hypertensive patients with or without renal failure. In healthy subjects neither a single dose of 10 mg carteolol nor continuous administration of 20 mg/day for 7 days had any effect on creatinine clearance and renal blood flow. In all subjects the clearance rate of carteolol was about 400 ml/min and its fractional excretion of carteolol exceeded 300%, suggesting that the drug is secreted actively from renal tubules. Twenty-three hypertensive patients with or without renal dysfunction were given carteolol 10 to 20 mg/day for more than 50 weeks in addition to their standard antihypertensive regimens, which were left changed. Laboratory results were compared with the mean values of 50 weeks before and after the addition of carteolol, and none, including plasma creatinine, blood urea nitrogen and electrolytes, were significantly changed. Neither the estimated glomerular filtration rate nor the effect of the drug on blood pressure changed significantly during this prolonged treatment. It is concluded that carteolol had no effect on renal function in healthy subjects and in hypertensive patients with or without renal failure.
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    URL: http://dx.doi.org/10.1007/BF00561030
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    Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 119-125 
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    ISSN: 1432-1041
    Keywords: co-dergocrine ; hypertension ; presynaptic dopamine2-receptors ; norepinephrine ; haemodynamic effects ; side-effects ; renin-angiotensin-aldosterone system ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by −7% and the upright plasma NE level by −24%. Supine plasma NE also fell (−24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by −6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL − cholesterol fraction.
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    URL: http://dx.doi.org/10.1007/BF00609182
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    Antihypertensive and hypouricaemic effects of nitrendipine in chronic renal failure (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 223-227 
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    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; hypertension ; uric acid excretion ; metabolic effects ; cardiovascular risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine. Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed. Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.
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    Responses of glomerular filtration, renal blood flow and salt-water handling to acute cardioselective and non-selective β-adrenoceptor blockade in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 343-345 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; pindolol ; renal haemodynamics ; salt-water handling ; hypertension ; beta-adrenoceptor blockade ; ISA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective β-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) β-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1–2 hypertensive men. M lowered pulse rate more than P. Systolic pressure was equally reduced by both agents, and diastolic and mean pressures were decreased only after P. Glomerular filtration rate was not significantly altered by either antagonist, and renal blood flow decreased by approximately 11% both after M and P. Renal vascular resistance was unchanged after P, and was increased by 10% after M. It is concluded that, like the effects on central haemodynamics, ISA is more important in the renal response to β-adrenoceptor blockade than is β-receptor selectivity.
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    URL: http://dx.doi.org/10.1007/BF00558292
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    Long-term effect of pindolol on lipids and lipoproteins in men with newly diagnosed hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 347-350 
    Details
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; hyperlipidaemia ; chronic treatment ; cholesterol ; HDL ; LDL ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension. Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension. Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year. The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol · l−1 during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year. It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment.
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    URL: http://dx.doi.org/10.1007/BF00558293
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    Antihypertensive effect of slow-release nicardipine. A placebo-controlled cross-over study (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 439-442 
    Details
    ISSN: 1432-1041
    Keywords: calcium antagonists ; nicardipine ; hypertension ; placebo effect ; slow-release preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the anti-hypertensive effect of slow-release nicardipine (SR-Nicardipine) have been compared with placebo in 36 uncomplicated essential hypertensives (diastolic BP 95 to 115 mm Hg after 1-month placebo washout). According to a double-blind, randomized, cross-over design they received SR-Nicardipine 40 mg b.d. and placebo for 1 month. At the end of each treatment period, blood pressure and heart rate were measured 12 h after the evening dose and 1, 2, 3 and 4 h after the morning dose. SR-Nicardipine significantly reduced systolic (SBP) and diastolic (DBP) blood pressure at each time after dosing. The absolute decrements peaked 4 h after dosing (−18.3 and −11.7 mm Hg, respectively) and more than 90% of the peak effect persisted 12 h after dosing, both for SBP and DBP. The heart rate was slightly increased by SR-Nicardipine. Adverse effects monitored with a check-list occurred in 31% of patients during SR-Nicardipine treatment and in 28% on placebo. Thus, SR-Nicardipine 40 mg b.d. has a maintained and significant antihypertensive effect lasting up to 12 h in essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00558066
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    Dependent oedema and attenuation of postural vasoconstriction associated with nifedipine therapy for hypertension in diabetic patients (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 333-335 
    Details
    ISSN: 1432-1041
    Keywords: diabetes mellitus ; nifedipine ; hypertension ; oedema ; vasodilator ; blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied the incidence of oedema 2 weeks following initation of nifedipine therapy for hypertension in a group of 10 diabetic subjects, and also measured skin blood flow (SBF) with a laser Doppler flowmeter, before and after lowering the foot. SBF with the foot horizontal increased after nifedipine from 0.31V (arbitrary units of flow) to 0.51V (NS). The postural fall in blood flow in dependency was significantly attenuated by nifedipine from 64.4 to 24.0%. Five patients developed ankle oedema. Results were similar in a small group of non-diabetic subjects starting nifedipine. The attenuation of reflex postural vasoconstriction is therefore likely to contribute to development of the oedema associated with starting nifedipine therapy, which should be monitored carefully in diabetic patients.
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    URL: http://dx.doi.org/10.1007/BF00558495
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  • 93
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    Comparative haemodynamic effects of ketanserin and ritanserin in the proximal and distal upper limb circulations of hypertensive patients (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 215-220 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; ritanserin ; hypertension ; haemodynamics ; alpha1-adrenoceptor blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of ketanserin (40 mg p.o.) on blood pressure and brachial haemodynamics (brachial artery diameter, brachial blood velocity and blood flow) have been compared in a double-blind study with those of ritanserin (10 mg p.o.) and placebo. Haemodynamic parameters were measured before and 1 h after treatment. Patients with mild to moderate essential hypertension participated in this study, 6 each on ketanserin, ritanserin and placebo. Placebo significantly reduced heart rate and did not modify the other parameters. Compared to placebo, ketanserin significantly reduced systolic and diastolic blood pressure, increased brachial blood velocity and flow, and decreased forearm vascular resistance. Compared to placebo, ritanserin slightly decreased blood pressure and slightly increased blood flow, but neither effect was significant. When blood circulation to the hand was excluded, neither ketanserin nor ritanserin modified the proximal arterial resistance or blood flow. It is concluded that the actions of ketanserin and ritanserin essentially occurred in the distal part of the upper limb, and alpha1-receptor blockade is probably involved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00679772
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  • 94
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    The effect of nisoldipine on renal function in the long-term treatment of hypertension in patients with and without renal impairment (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 437-441 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; renal function/-impairment ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of nisoldipine on renal function after 6 weeks treatment was investigated in hypertensive patients with and without renal impairment. Nisoldipine was well tolerated and an effective antihypertensive agent when administered over a period of 6 weeks. There were no significant changes in glomerular filtration, cardiac output, plasma renin activity or serum biochemistry during nisoldipine administration. Effective renal plasma flow was unaffected by treatment in the patients with normal renal function, but in the patients with renal insufficiency, the value decreased by a mean of 12%. Nisoldipine had no major untoward effects on renal function after 6 weeks administration, but minor changes in renal haemodynamics in the patients with renal insufficiency would suggest that careful monitoring of renal function is indicated in such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558120
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  • 95
    Electronic Resource
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    Once daily nisoldipine in hypertension: cuff and ambulatory intra-arterial blood pressure (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 551-554 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; ambulatory monitoring ; cuff blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cuff blood pressure data has suggested that the calcium channel antagonist nisoldipine has full twenty four hour efficacy. To test this, 24 h ambulatory intra-arterial blood pressure monitoring was performed on 18 untreated hypertensive subjects (12 men, 6 women) (cuff blood pressure 〉150/95 mm Hg) before and after chronic treatment with 10–20 mg oral nisoldipine taken daily at 08.00 h. Twelve patients completed the study, six being withdrawn, four because of side-effects. After baseline intra-arterial monitoring patients were started on 10 mg nisoldipine daily. Response was assessed by cuff pressures taken 24 h after dosing at fortnightly intervals, and if not controlled (〈150/95 or at least 10 mm Hg reduction in diastolic BP) the dose was increased to 20 mg. All patients received at least six weeks' therapy before the second intra-arterial blood pressure monitoring. There was a slight but insignificant reduction in mean daytime heart rate of 3 beats·min−1. Mean significant reduction in daytime systolic and diastolic BP was 19 mm Hg and 13 mm Hg respectively but there was no significant mean night-time reduction. By comparison 8 out of 12 patients were apparently controlled more than 24 h post dose according to cuff pressures. This study suggests that this formulation of nisoldipine does not control blood pressure over a full 24-h period, and emphasises the importance of 24 h ambulatory monitoring in assessing the efficacy of once-daily antihypertensive agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562542
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  • 96
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    Membrane transport and disease (1989)
    Springer
    Molecular and cellular biochemistry 91 (1989), S. 3-11 
    Details
    ISSN: 1573-4919
    Keywords: calcium ATPase ; glucose transport ; herpes virus ; hypertension ; leaks ; pore-formation ; sodium channels ; stress ; toxins ; transport ; viruses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Four situations in which membrane transport is altered by disease are discussed: (a) non-specific leaks induced by poreforming agents; (b) glucose transport and cellular stress; (c) Ca+-ATPase and hypertension; (d) Na− channels and HSV infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228073
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  • 97
    Electronic Resource
    Electronic Resource
    Hemodynamics in emotional responses and in emotional stress (1989)
    Springer
    Neuroscience and behavioral physiology 19 (1989), S. 399-407 
    Details
    ISSN: 1573-899X
    Keywords: hemodynamics ; stress ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract In the article, we present experimental data indicating that negative emotional states evoked by electrical stimulation of the ventromedial hypothalamus or by behavioral conflicts are accompanied by a predominance of vascular responses of a presser character possessing the property of summation. In contrast, positive emotional states during a self-stimulation reaction or when animals attain behavioral results satisfying their major biological demands are accompanied by a predominance of pressor-depressor vascular reactions. In individual animals under conditions of experimental emotional stress in conflicting situations of a prolonged character, pronounced disturbances of cardiac-vascular functions occur. Predominantly pressor vascular reactions arise in response to forced stimulation of the ventromedial hypothalamus in such cases. It is shown that changes in vascular tonus plays a leading role in disturbances of AP regulation during stress of immobilization. The most frequent cause of death in animals under such conditions is a progressive fall of AP due to an abrupt decrease in the total peripheral resistance. The resistance of the cardiac-vascular functions to emotional stress is determined to a significant degree by genetic mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01197872
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  • 98
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    Electronic Resource
    Platelet Na+/H+ exchange in spontaneously hypertensive rats (1989)
    Springer
    Bulletin of experimental biology and medicine 107 (1989), S. 200-202 
    Details
    ISSN: 1573-8221
    Keywords: hypertension ; platelets ; sodium-proton exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00833802
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  • 99
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    Permeability of erythrocyte membranes for monovalent cations (Na+, K+) and their transformation in essential symptomatic (renal) hypertension (1989)
    Springer
    Bulletin of experimental biology and medicine 107 (1989), S. 632-635 
    Details
    ISSN: 1573-8221
    Keywords: hypertension ; erythrocyte membrane permeability ; electron microscopy ; erythrocyte transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00841769
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  • 100
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    Electronic Resource
    Course of wound healing in spontaneously hypertensive rats under the influence of morphine, substance P, and its SP1–4 fragment (1989)
    Springer
    Bulletin of experimental biology and medicine 107 (1989), S. 867-871 
    Details
    ISSN: 1573-8221
    Keywords: wound healing ; morphine ; hypertension ; substance P
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00840765
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