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  • Rat  (599)
  • Immunocytochemistry  (357)
  • hypertension  (282)
  • Springer  (1,207)
  • American Chemical Society
  • 1985-1989  (618)
  • 1980-1984  (455)
  • 1970-1974  (134)
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  • 1
    Electronic Resource
    Electronic Resource
    Identification of brain tumours in rats using laser-induced fluorescence and haematoporphyrin derivative (1989)
    Springer
    Lasers in medical science 4 (1989), S. 241-249 
    Details
    ISSN: 1435-604X
    Keywords: Brain tumour ; Rat ; Detection ; Fluorescence ; Laser ; Haematoporphyrin derivative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Laser-induced fluorescence has been used for the identification of brain tumours in rats, which have been previously given tumour-seeking haematoporphyrin derivative. A pulsed nitrogen laser (λ=337 nm) was used in conjunction with an optical multichannel analyzer. For both inoculated RG-2 and TCVC rat-brain-tumour models, the blue autofluorescence was strongly reduced in the tumour compared with normal brain tissue, and at the same time the characteristic red-drug signal increased. The contrast between tumour and normal tissue was strongly enhanced by forming the ratio between the two signals. Implications for possible improvement of tumour delineation in brain tumour surgery are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02032454
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  • 2
    Electronic Resource
    Electronic Resource
    Corticotropin releasing factor increases the adrenocortical responsiveness to adrenocorticotropin (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1004-1006 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; adrenocortical responsiveness ; ACTH ; plasma ; corticosterone ; plasma ; corticotropin releasing factor (CRF)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 μg compared with 5 μg per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p〈0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946481
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  • 3
    Electronic Resource
    Electronic Resource
    Occurrence, distribution and nature of neuropeptide Y in the rat pancreas (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1554-1557 
    Details
    ISSN: 1420-9071
    Keywords: Immunocytochemistry ; neuropeptide Y ; radioimmunoassay ; rat pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Significant quantities of a newly discovered peptide, neuropeptide Y, were found in the rat pancreas, where they were localized to nerves in the exocrine parenchyma and around arterial and ductal structures. Although unaffected by surgical parasympathectomy, the periarterial and periductal nerves were abolished by chemical sympathectomy, suggesting that NPY is partially costored with sympathetic transmitters in nerve fibers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01964804
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of hydrochlorothiazide on the pain threshold and on the antinociceptive activity of morphine, in rats (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 265-266 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; hydrochlorothiazide ; pain threshold ; antinociceptive activity ; analgesic activity ; morphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02002628
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  • 5
    Electronic Resource
    Electronic Resource
    Do prostaglandins mediate the somatostatin preventive effect on gastric lesion? (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 974-975 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; prostaglandins ; gastric lesion ; intragastric distension model ; stress model ; indomethacin ; somatostatin preventive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946466
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  • 6
    Electronic Resource
    Electronic Resource
    Rate of normal longitudinal bone growth in the rat (1972)
    Springer
    Calcified tissue international 10 (1972), S. 238-251 
    Details
    ISSN: 1432-0827
    Keywords: Growth ; Bone ; Rat ; Tetracycline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La vitesse de croissance normale en longueur de la métaphyse proximale du tibia est déterminée chez le rat Sprague-Dawley entre les âges de 20 et 100 jours, en utilisant la méthode à la tétracycline. Le taux de croissance ne varie que légèrement dans les groupes d'âges différents. Il est plus élevé chez les animaux jeunes et décroit considérablement en fonction de l'augmentation de l'âge. Les rats mâles présentent une croissance plus élevée que les femelles. Cette étude a pour but de mettre au point une méthode permettant de déterminer les facteurs expérimentaux, liés à la croissance en longueur du rat.
    Abstract: Zusammenfassung Die normale Längenwachstums-Geschwindigkeit der proximalen Wachstumsplatte der Tibia wurde bei Sprague-Dawley-Ratten in einem Alter zwischen 20 und 100 Tagen mittels der Tetracyclinmethode gemessen. Die Wachstumsgeschwindigkeit variierte nur wenig innerhalb der einzelnen Altersgruppen. Die Geschwindigkeit war bei jungen Tieren am höchsten und nahm mit zunehmendem Alter beträchtlich ab. Männliche Ratten wuchsen schneller als weibliche. Diese Arbeit dient als Grundlage, um die experimentelle Beeinflussung des Längenwachstums der Ratte abschätzen zu können.
    Notes: Abstract The rate of normal growth in length from the proximal growth plate of the tibia in the Sprague-Dawley rat was measured between 20 and 100 days of age using the tetracycline method. The growth rate varied only slightly within different age groups. The rate was highest in young animals and decreased considerably with increasing age. Male rats grew faster than female. This study is intended to provide a base for an evaluation of experimental influence on the growth in length of the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02012553
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  • 7
    Electronic Resource
    Electronic Resource
    Extracellular localization of cathepsin D in ossifying cartilage (1973)
    Springer
    Calcified tissue international 12 (1973), S. 313-321 
    Details
    ISSN: 1432-0827
    Keywords: Cathepsin D ; Extracellular ; Ossification ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé De la cathepsine D extracellulaire d'origine principalement ostéoblastique a été démontrée par immunohistochimie dans le cartilage en voide de calcification de cultures d'os des membres d'embryons de poulet. L'intérêt de ce fait pour l'ossification est discuté.
    Abstract: Zusammenfassung Es wurde mit einer immunohistochemischen Methode gezeigt, daß extrazelluläres Kathepsin D, welches hauptsächlich aus Osteoblasten gewonnen wurde, Knorpel von kultivierten Knochen von Kükenembryonen mineralisiert. Die Bedeutung dieser Feststellung für den Mechanismus der Knochenbildung wird diskutiert.
    Notes: Abstract Extracellular cathepsin D derived mainly from osteoblasts has been demonstrated immunohistochemically in ossifying cartilage of cultured embryonic chick limb bones. The relevance of this observation to the mechanism of ossification is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02013744
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  • 8
    Electronic Resource
    Electronic Resource
    Immunological homologies between yeast ribosomal protein L2 and rat liver ribosomal proteins L4 and L24 (1988)
    Springer
    Current genetics 13 (1988), S. 235-239 
    Details
    ISSN: 1432-0983
    Keywords: Ribosomal protein ; Immunological homology ; Yeast ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Polyclonal antibodies raised against ribosomal protein (r-protein) L2 of Schizosaccharomyces pombe were used to check for cross-reaktions with total r-proteins of rat liver. Using this procedure, the rat liver r-proteins, L4 and L24, were identified as being immunologically related to yeast L2. In addtional, homologies between rat liver L4 and L24 were detected. The possible implications for the regulation of r-protein synthesis are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387769
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  • 9
    Electronic Resource
    Electronic Resource
    Intra- and interspecies analyses of the carcinoembryonic antigen (CEA) gene family reveal independent evolution in primates and rodents (1989)
    Springer
    Journal of molecular evolution 29 (1989), S. 126-134 
    Details
    ISSN: 1432-1432
    Keywords: Carcinoembryonic antigen ; Evolution ; Gene family ; Human ; Rat ; Synonymous substitutions ; Silent molecular clock ; Evolutionary trees
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02100111
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  • 10
    Electronic Resource
    Electronic Resource
    Qualitative and quantitative variability in different classes of proteins: Comparison of mouse and rat (1987)
    Springer
    Journal of molecular evolution 24 (1987), S. 260-271 
    Details
    ISSN: 1432-1432
    Keywords: Mouse ; Rat ; Two-dimensional electrophoresis ; Quantitative variability of proteins ; Qualitative variability of proteins ; Protein classes ; Membrane proteins ; Organ-specific proteins ; Regulatory genes ; Speciation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Proteins of membranes and cytosols were extracted from the livers and brains of mice (inbred strain DBA/6J) and rats (inbred strain DA/Han) and separated by two-dimensional electrophoresis (2-DE). The 2-DE patterns were compared with regard to qualitative (spot position) and quantitative (spot intensity) characteristics of the proteins of these two species. The following results were obtained: (1) Brain had more (higher percentage) conservative proteins (proteins found in both mice and rats) than liver; (2) plasma membranes had more conservative proteins than the cytosols; (3) organ-unspecific proteins contained more conservative proteins than relatively organ-specific proteins; (4) the pattern of distribution of genetic variability among different classes of proteins represented by findings 1–3 was the same for the qualitative and quantative characteristics of the proteins; and (5) some observations indicated that quantitative variability occurred more frequently among proteins than did qualitative variability. Our conclusion is that regulatory sequences in the DNA (regulatory genes) are subjected to functional constraints that differ in strength among different classes of proteins by the same ratios as the constraints acting on the structural genes. The overall effect of the selective pressure is, however, less stringent for regulatory genes than for structural genes. The results obtained here by comparing two different species are very similar to previous results we obtained by studying different subspecies (inbred strains of the mouse). From this finding arises a new concept: the study of molecular evolution on the basis of different classes of proteins. Our results were compared with data from the literature that were obtained in part from studies on cultured cells. The comparison suggested that cultured cells have lost their tissue-specific proteins, and so generate predominantly extremely conservative proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02111239
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  • 11
    Electronic Resource
    Electronic Resource
    Distribution of vitamin A in various organs of rats in relation to the quality and the quantity of dietary proteins (1987)
    Springer
    European journal of nutrition 26 (1987), S. 43-51 
    Details
    ISSN: 1436-6215
    Keywords: Dietary protein ; Vitamin A ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Es wurde der Einfluß von Qualität und Quantität von Nahrungsproteinen auf die Verteilung einer einzigen massiven Dosis von Vitamin A in verschiedenen Organen wachsender Wistar-Ratten untersucht. Die Untersuchungen wurden mit Casein- und Bengal-Gram-Diäten mit 20 % und 10 % Proteingehalt und auch mit radioaktiv markiertem Retinylacetat durchgeführt. Die Ergebnisse zeigen, daß die Leberspeicherung sowohl von Vitamin A aus der Nahrung als auch die einer einzigen starken Vitamin-A-Gabe (20 000 I.U.) stark herabgesetzt war bei Ratten, die nach der Bengal-Gram-Diät gefüttert wurden, verglichen mit Ratten, die auf Casein-Diät gesetzt waren. Im Gegensatz zur Leberspeicherung ist das Vitamin-A-Niveau im Plasma in allen Gruppen vergleichbar. Füttern niedriger Protein-Qualität reduzierte die Gewebeverteilung von [3H]-Retinylacetat sowohl bei Kontrollratten als auch bei solchen, denen eine massive Dosis Vitamin A gegeben wurde. Diese Untersuchung läßt vermuten, daß sowohl schlechte Qualität als auch unzureichende Mengen von Nahrungsproteinen nachteilige Einflüsse auf den Vitamin-A-Zustand wachsender Ratten haben.
    Notes: Summary The influence of the quality and the quantity of dietary proteins on the distribution of a single massive dose of vitamin A in various organs of growing Wistar strain rats has been studied by using casein and bengal gram diets at 20 % and 10 % protein levels. The distribution of [3H]-retinyl acetate in various tissues was also investigated in these dietary conditions. The results show that the hepatic storage of dietary as well as a single massive dose (20,000 I.U.) of vitamin A was profoundly decreased in the rats fed on bengal gram diets as compared to those fed on casein diets. Regardless of hepatic stores, the plasma vitamin A levels were comparable in all the groups. Feeding of low quality of protein reduced the tissue distribution of [3H]-retinyl acetate in control as well as rats given a massive dose of vitamin A. This study suggests that both the poor quality and the inadequate quantity of dietary protein are detrimental influences on the vitamin A status of the growing rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02023818
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  • 12
    Electronic Resource
    Electronic Resource
    Immunocytochemical location of vitellin in the egg of the silkworm,Bombyx mori, during early developmental stages (1983)
    Springer
    Development genes and evolution 192 (1983), S. 113-119 
    Details
    ISSN: 1432-041X
    Keywords: Vitellin ; Yolk granule ; Yolk protein ; Silkworm ; Embryogenesis ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Vitellin was purified from eggs of the silkworm,Bombyx mori, by a new method in which vitellin was extracted from isolated yolk granules. The purified vitellin had a molecular weight of 540,000. An antibody against purified vitellin was prepared in rabbits. It reacted with the hemolymph vitellogenin as well as with purified vitellin, but not with other proteins in the hemolymph or in the extract from yolk granules. The anti-vitellin IgG was used to immunocytochemically locate vitellin in theBombyx non-diapause egg during early developmental stages. In the egg, just after oviposition, vitellin was located in internal yolk granules and in small yolk granules of the periplasm. During the early developmental stages studied, vitellin was not metabolized uniformly throughout the egg. The vitellin of the internal yolk granules located at the posterior-dorsal part and of the small peripheral yolk granules was utilized in 16 h and 2 days, respectively, after oviposition. A thin, very vitellin-poor layer was located between the periplasm and the vitellin-rich interior in the newly laid egg. it was always in close contact with the periphery where blastoderm and germ-band cells developed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848679
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  • 13
    Electronic Resource
    Electronic Resource
    Tall gut formation in the rat embryo (1985)
    Springer
    Development genes and evolution 194 (1985), S. 429-432 
    Details
    ISSN: 1432-041X
    Keywords: Tail bud ; Tail gut ; Gut ; Organogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The formation of the tail portion of the primitive gut was investigated by light and electron microscopy in 10- and 11-day rat embryos. The observations permit the conclusion that the tail gut does not form as a posterior extension of the hindgut but originates from the tail bud mesenchyme by mechanism analogous to the secondary neurulation. It includes cell condensation, aquisition of apicobasal polarity and the radial, rosette-like arrangement around a central cavity. These cells bear the cytological characteristics of both the absorptive epithelial cells and the mesenchymal cells at their apical (adluminal) and abluminal ends respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848557
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  • 14
    Electronic Resource
    Electronic Resource
    Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1365-1366 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; cerebrospinal fluid, human ; analgesia ; naloxone ; pain indifference, congenital ; opiates, endogenous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01951891
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  • 15
    Electronic Resource
    Electronic Resource
    15-Hydroxyprostaglandin dehydrogenase and hexokinase in spontaneously hypertensive rat kidney (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1368-1369 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; kidney ; hypertensive ; prostaglandin dehydrogenase ; hexokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01951893
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  • 16
    Electronic Resource
    Electronic Resource
    Changes in brush-border enzyme activities of intestinal epithelial cells isolated from the villus-crypt axis during the early phase of alloxan diabetes in rats (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 482-484 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; alloxan diabetes ; intestinal villus ; alkaline phosphatase ; sucrase ; epithelial cells ; villus-crypt axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The sucrase activity in enterocytes isolated from the villus crypt axis was found to increase in all regions of the villus from day 2 after induction of diabetes, and the increase continued until day 4. In contrast, alkaline phosphatase activity increased mainly in the apical one-third of the villus-crypt column, and the increase occurred abruptly on day 4 with increase in food intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01966159
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  • 17
    Electronic Resource
    Electronic Resource
    Basal plasma corticosterone level after bilateral selective lesions of thee olfactory pathways in the rat (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 169-171 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; olfactory pathway selective lesions ; plasma corticosterone ; lactacidemia ; adrenal glands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In comparison to control rats, basal plasma corticosterone level and lactacidemia significantly increased in rats submitted to a bilateral lesion of the lateral olfactory tract and/or the anterior branch of the anterior commissure. Only the anterior branch of the anterior commissure induced hyperglycemia; that of the lateral olfactory tract exerted an opposite effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01952451
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  • 18
    Electronic Resource
    Electronic Resource
    Development of high blood pressure in spontaneously hypertensive rats is delayed by treatment with cyclosporin at an early age (1987)
    Springer
    Cellular and molecular life sciences 43 (1987), S. 403-405 
    Details
    ISSN: 1420-9071
    Keywords: SHR ; cyclosporin ; immune mechanisms ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In spontaneously hypertensive rats the effect of the T-cell inhibitor cyclosporin was studied at different ages. If treatment was started at the age of 2 weeks the development of hypertension was delayed, but the ultimate level of blood pressure was not affected. These results indicate the involvement of immune mechanisms in the early development of hypertension in spontaneously hypertensive rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01940428
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  • 19
    Electronic Resource
    Electronic Resource
    Immunocytochemical and electrophoretic studies on the localization of the major haemolymph proteins (ceratitins) inCeratitis capitata during development (1984)
    Springer
    Development genes and evolution 194 (1984), S. 37-43 
    Details
    ISSN: 1432-041X
    Keywords: Major haemolymph proteins ; Development ; Cuticle ; Immunocytochemistry ; Ceratitis capitata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The developmental profile of the major haemolymph proteins (ceratitins) inCeratitis capitata was studied. Ceratitin concentration in the haemolymph decreases dramatically during the last days of pupal life, while the amounts of ceratitins in whole organism extracts remain unchanged. By electrophoretic, immunological and immunofluorescence techniques it was revealed that ceratitins are reabsorbed by the fat body and a fraction of them is deposited in the cuticle. The possible role of ceratitins is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00848952
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  • 20
    Electronic Resource
    Electronic Resource
    Ethanol preference in rats with a prior history of acetaldehyde self-administration (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1008-1010 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; ethanol preference ; acetaldehyde self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Peripherally self-injected acetaldehyde in interaction with environmental and nutritional variables significantly enhances alcohol drinking in rats and suggests an involvement of acetaldehyde in voluntary alcohol intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01946483
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  • 21
    Electronic Resource
    Electronic Resource
    Immunocytochemical demonstration of calmodulin in cells secreting by exocytosis (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1340-1342 
    Details
    ISSN: 1420-9071
    Keywords: Immunocytochemistry ; calmodulin ; secretory granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreaticβ-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01952085
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  • 22
    Electronic Resource
    Electronic Resource
    Effects of β-hydroxybutyrate on rat embryos grown in culture (1985)
    Springer
    Cellular and molecular life sciences 41 (1985), S. 273-275 
    Details
    ISSN: 1420-9071
    Keywords: Rat ; embryo ; embryo ; rat ; β-hydroxybutyrate ; diabetes ; maternal ; fetal malformation ; malformation ; fetal ; ketone bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In order to investigate further the relationship between maternal diabetes and fetal malformation, rat embryos were grown in vitro in the presence of β-hydroxybutyrate, one of the ketone bodies produced by diabetics. At 10 mM, β-hydroxybutyrate produced minor abnormalities and at 20 mM it produced major abnormalities in rat embryos.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02002633
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  • 23
    Electronic Resource
    Electronic Resource
    Kinins in cerebrospinal fluid: Reduced concentration in spontaneously hypertensive rats (1986)
    Springer
    Cellular and molecular life sciences 42 (1986), S. 1238-1239 
    Details
    ISSN: 1420-9071
    Keywords: Kinins ; bradykinin ; kallidin ; cerebrospinal fluid ; HPLC ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rat cerebrospinal fluid contains peptides which displace radiolabeled bradykinin from its specific antibodies. Two peptides which showed the same retention time as kallidin and bradykinin in a reverse phase high pressure liquid chromatography system were detected in cerebrospinal fluid of rats. The concentration of radioimmunologically detected kinins in the cerebrospinal fluid of spontaneously hypertensive rats of the Okamoto strain was lower than that of the Wistar Kyoto control rats.
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    The effects of sodium fluoride on bone breaking strength (1974)
    Springer
    Calcified tissue international 14 (1974), S. 283-289 
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    ISSN: 1432-0827
    Keywords: Sodium fluoride ; Osteoporosis ; Bone ; Strength ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'utilisation thérapeutique de fluorure de sodium a été recommandée dans le traitement de diverses maladies osseuses ostéopéniques. Cet emploi est basé principalement sur les effects ostéosclérotiques bien connus du fluorure de sodium, mais on connait mal son effet sur la force de résistance osseuse. L'influence de diverses concentrations de fluorure de sodium sur la force de résistance osseuse de jeunes rats soumis à des régimes riches et pauvres en calcium a été étudiée. L'administration de fluorure de sodium augmente le diamètre osseux, indiquant une stimulation de la formation de l'os périosté, mais la force de résistance osseuse est réduite ou non modifiée par l'ingestion de fluor.
    Abstract: Zusammenfassung Die therapeutische Verwendung von Natriumfluorid ist für eine Anzahl von Knochenmangel-Krankheiten empfohlen worden. Die Empfehlungen basieren hauptsächlich auf den bekannten osteosklerotischen Wirkungen von Natriumfluorid; über dessen Effekt auf die Knochenstärke ist wenig bekannt. In dieser Arbeit wurde der Einfluß verschiedener Konzentrationen von Natriumfluorid auf die Knochenstärken von wachsenden Ratten mit hoher und niederer Calciumeinnahme untersucht. Die Verabreichung von Natriumfluorid erhöhte den Knochendurchmesser, was auf eine Stimulierung der Periostbildung hinwies, die Knochenstärke wurde jedoch durch Fluorideinnahme herabgesetzt oder nicht beeinflußt.
    Notes: Abstract The therapeutic use of sodium fluoride has been recommended in a variety of osteopenic bone diseases. The recommendations are based mainly on the known osteosclerotic effects of sodium fluoride and little information is available as to its effect on bone strength. The influence of various concentrations of sodium fluoride on bone strength in growing rats on high and low calcium diets was studied. The administration of sodium fluoride increased bone diameter, indicating stimulation of periosteal bone formation, but bone strength was reduced or not affected by fluoride ingestion.
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    Cell kinetics and morphology of the growth plate in the normal and hypophysectomized rat (1973)
    Springer
    Calcified tissue international 13 (1973), S. 113-129 
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    ISSN: 1432-0827
    Keywords: Kinetics ; Growth ; Epiphyses ; Hypophysectomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé La largeur de la métaphyse tibiale, la zone indifférenciée, la zone sériée et les cellules en dégénerescence ont été observées chez des rats Sprague-Dawley normaux et hypophysectomisés. La production cellulaire de la métaphyse est déterminée sur la base de la croissance osseuse longitudinale déterminée par l'oxytétracycline et la taille des cellules en dégénérescence. La diminution de la croissance osseuse longitudinale, en fonction de l'augmentation de l'âge et après hypophysectomie, est due partiellement, à la diminution de production cellulaire et partiellement à une décroissance de la taille des cellules en dégénérescence dans la métaphyse. L'influence de la production cellulaire et de l'activité mitotique prédomine.
    Abstract: Zusammenfassung Die Breite der proximalen Wachstumsplatte der Tibia, deren undifferenzierter und säulenförmiger Zone und die Größe der nahe bei der Metaphyse auftretenden degenerativen Zellen wurden in normalen und hypophysektomierten Sprague-Dawley-Ratten bestimmt. Die Zellproduktion in der Wachstumsplatte wurde aus dem longitudinalen Knochenwachstum berechnet, welches mittels Oxytetracyclin und der Größe der degenerativen Zellen bestimmt wurde. Es wurde festgestellt, daß die Abnahme des longitudinalen Knochenwachstums bei zunehmendem Alter und nach Hypophysektomie zum Teil einem Rückgang in der Zellproduktion, zum Teil einer Verminderung der Größe der degenerativen Zellen in der Wachstumsplatte zuzuschreiben ist. Der Einfluß der Zellproduktion, und somit der mitotischen Aktivität, herrscht vor.
    Notes: Abstract The width of the proximal growth plate of the tibia, its undifferentiated and columnar zone and the size of the degenerative cell close to the metaphysis, were determined in normal and hypophysectomized Sprague-Dawley rats. The cell production in the growth plate was calculated from the longitudinal bone growth determined with oxytetracycline and the degenerative cell size. It was found that the decrease in longitudinal bone growth with increasing age and after hypophysectomy, is due partly to a decrease in cell production, and partly to a decrease in degenerative cell size in the growth plate. The influence of cell production and thus the mitotic activity predominates.
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    Fine structure of fetal rat calvarium; provisional identification of preosteoclasts (1980)
    Springer
    Calcified tissue international 31 (1980), S. 21-28 
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    ISSN: 1432-0827
    Keywords: Rat ; Calvarium ; Electron microscopy ; Preosteoclasts ; Osteoclasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary This is a study of the fine structure of cells of the 20-day fetal rat calvarium. Special attention is given to identifying and characterizing preosteoclasts. These cells are relatively common and located largely, but not exclusively, at the endocranial bone surface. The preosteoclasts are characterized by abundant mitochondria, an incomplete perinuclear Golgi apparatus, and variable-shaped dense granules. The dense granules are unique in appearance in that they contain an internal dense matrix surrounded by a clear halo. Most granules are circular in shape but some are elongate or tubular in form. Granules with identical appearance are observed in osteoclasts. The preosteoclasts are mononucleate, or occasionally binucleate. It is suggested that because preosteoclasts are morphologically distinctive and relatively abundant, it should be feasible to separate these cells from a heterogeneous cell isolate.
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    URL: http://dx.doi.org/10.1007/BF02407163
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    Correlation of45Ca incorporation with maturation ameloblast morphology in the rat incisor (1982)
    Springer
    Calcified tissue international 34 (1982), S. 211-213 
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    ISSN: 1432-0827
    Keywords: Rat ; incisor ; ameloblasts ; enamel ; 45Ca autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Rats were injected with45Ca and horseradish peroxidase to determine the patterns of45Ca incorporation into incisor enamel and the morphological types of the overlying maturation ameloblasts.45Ca autoradiography showed no differences in the patterns of incorporation into enamel between routinely embedded and freeze-dried specimens. Enamel overlaid by ruffle-ended ameloblasts was much more heavily labeled while that overlaid by smooth-ended ameloblasts showed only moderate labeling. The observations lend further support to the hypothesis that the ruffle-ended cells are very active in mineralizing enamel and that the smooth-ended cells are in a passive, restorative phase.
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    Effect of vitamin D deficiency on urinary excretion of connective tissue derivatives (hydroxyproline and glycosaminoglycans) in rats (1981)
    Springer
    Calcified tissue international 33 (1981), S. 177-180 
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    ISSN: 1432-0827
    Keywords: Connective Tissue ; Vitamin D deficiency ; Hydroxyproline excretion ; Glycosaminoglycan excretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The urinary excretion of two connective tissue metabolites was studied in both control and vitamin D deficient rats. Hydroxyproline (HyPRO) excretion was determined after 2, 13 and 22 months (experiment I). It decreased with aging in animals receiving the control diet. On the contrary, this excretion increased as a function of age in vitamin D deficient animals. At the age of 22 months, HyPRO excretion was respectively 31 and 1708 µg a day in control and deficient animals. HyPRO and glycosaminoglycans (GAG) excretion was measured on a group of both control and vitamin D deficient rats at the age of 21 months (experiment II). These results confirm the high excretion of HyPRO in deficient animals. On the contrary, the GAG excretion was higher in control animals than in deficient ones, the mean excretion being respectively 412 and 234 µg a day.
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    URL: http://dx.doi.org/10.1007/BF02409432
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    An automatic microspectrophotometric scanning method for the measurement of bone formation rates in vivo (1980)
    Springer
    Calcified tissue international 32 (1980), S. 63-68 
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    ISSN: 1432-0827
    Keywords: Rat ; Bone formation ; Fluorochrome ; Microphotometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A method for quantitative studies of the formation rate of bone has been developed. After vital staining with calcein, the fluorescence of a bone section was measured with a microphotometer controlled by a mini computer. After staining the bone structure with alizarin red S in a second step, the section was measured in transmitted light. The two data sets were combined and the shortest distances between the bone surface and the fluorescence lines were computed. With this information the distance distribution and the bone area between the label and the surface could be calculated in two different ways: with the single labeling and the continuous labeling techniques. The advantages and disadvantages of the two methods are discussed and compared with those of other techniques.
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    URL: http://dx.doi.org/10.1007/BF02408522
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    A quantitative histologic analysis of the growing long bone metaphysis (1980)
    Springer
    Calcified tissue international 32 (1980), S. 113-122 
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    ISSN: 1432-0827
    Keywords: Rat ; Bone ; Metaphysis ; Quantitative ; Aging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 µm thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.
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    Role of growth hormone in experimental phosphorus deprivation in the rat (1980)
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    Calcified tissue international 32 (1980), S. 105-112 
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    ISSN: 1432-0827
    Keywords: Rat ; Hypophysectomy ; Dietary phosphorus deprivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of45Ca rose; and (c) external P balance was restored and duodenal sac uptake of32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.
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    Effects of chronic protein deficiency on skeletal development of young rats (1981)
    Springer
    Calcified tissue international 33 (1981), S. 223-231 
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    ISSN: 1432-0827
    Keywords: Protein deficiency ; Bone formation ; Skeletal development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Protein deficiency was produced by freely feeding young rats a 1% lactalbumin diet for 12 weeks in order to study the effects of protein-calorie malnutrition on skeletal development. During the experiment the food and caloric intake and weight of the experimental animals decreased, while those parameters of the control animals progressively increased. However, when gross caloric intake was expressed as a function of the metabolic size of the animal, the caloric consumption was similar for both groups of animals. The protein-deficient animals exhibited micro-radiographic and histological features of an abnormal pattern of endochondral bone formation. Appositional bone growth, as determined by the daily appositional rate and the percentage of endosteal surfaces undergoing active bone formation, was significantly decreased in these animals, as was the percentage of periosteal surfaces exhibiting resorption. Both chemical analyses of the whole bone and electron probe microanalysis in the specific area of actively calcifying bone revealed no significant differences between the mineral content of control and protein-deficient animals. This study distinguishes the effects of protein deficiency from that of combined protein-calorie deprivation and demonstrates that the abnormal skeletal development observed was the result of a decrease in the quantity of bone formed rather than an altered mineral content.
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    Cytochemical studies on the ferritin-containing vesicles of the rat incisor ameloblasts with special reference to the acid phosphatase activity (1981)
    Springer
    Calcified tissue international 33 (1981), S. 51-55 
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    ISSN: 1432-0827
    Keywords: Rat ; Incisor ; Amelogenesis ; Acid phosphatase ; Ferritin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Acid phosphatase was localized in rat incisor ameloblasts without prior decalcification. Whenβ-glycerophosphate was used as the substrate, an intense reaction was observed in the supranuclear region of the secretory ameloblasts. But the reaction was dramatically reduced at the transitional stage and was very weak in the maturation ameloblasts. Whenp-nitrophenylphosphate was the substrate, the reaction product was consistently seen in the Golgi cisternae and the vesicular components of the ameloblasts at all stages of enamel development. These observations suggest that there are two acid phosphatases in ameloblasts. One is in the secretory ameloblasts and the other in the transition and maturation ameloblasts. X-ray micro-analyses for Fe and Pb showed that Fe and acid phosphatase were in the ferritin-containing vesicles at the later stage of enamel maturation. This evidence suggests that ferritin is digested in these vesicles for the release of the Fe pigment to the enamel. An increase in the number of intercellular bridges between ameloblasts was correlated with the dramatic decrease in height of ameloblasts at the pigment release stage. The ameloblast membranes were acid phosphatase positive at the intercellular bridges whenp-nitrophenylphosphate was the substrate. This activity may be involved in the reduction in the surface area of the ameloblast membranes.
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    Occurrence of actin-like protein in extracellular matrix vesicles (1982)
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    Calcified tissue international 34 (1982), S. 376-381 
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    ISSN: 1432-0827
    Keywords: Matrix vesicles ; Bone ; Actin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Preliminary indications of the occurrence of actin and myosin in crude matrix vesicle preparations have been reported previously. In the present study extracellular matrix vesicles from rat alveolar bone were isolated. They were further purified by a sucrose density gradient. SDS-polyacrylamide gel electrophoresis of the purified vesicles revealed the presence of a polypeptide with a molecular weight of 43 K daltons and with electrophoretic mobility identical to that of blood platelet actin. The limited proteolysis of both 43 K dalton vesicular polypeptide and actin byStaphylococcus aureus-V8-protease revealed three fragments with identical electrophoretic mobility. In addition, the vesicular preparations inhibited the activity of DNase I, a property typical of actin monomers. Filamentous material extracted from matrix vesicles showed ultrastructural features of F-actin. Reaction of this material with heavy meromyosin resulted in arrowhead formation, which is characteristic of acto-heavy meromyosin. The occurrence of actin in extracellular matrix vesicles may account for their budding from the osteoblastic plasma membrane, their possible motility in the matrix, and maintenance of the spherical shape.
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    Oral 1,25(OH)2D3: An effective prophylactic treatment for glucocorticoid osteopenia in rats (1983)
    Springer
    Calcified tissue international 35 (1983), S. 107-110 
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    ISSN: 1432-0827
    Keywords: Calcium ; Glucocorticoid ; Vitamin D ; Osteoporosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Eighty-eight adult male Sprague-Dawley rats were given a diet with either (a) 0.5% Ca and 0.6% P or (b) 0.01% Ca and 0.6% P. Osteopenia was created by adding prednisolone to the diet. The prophylactic effect of oral 1,25(OH)2D3 on the osteopenia was studied. It was found that prednisolone osteopenia in the rat was associated with defective Ca absorption. By giving an oral dose of 1,25(OH)2D3, it was possible to maintain normal Ca absorption during prednisolone treatment and to prevent the bone loss. No significant hypercalcemia or any kidney calcifications were seen. These results are in contrast to earlier findings, in which subcutaneous administration of 1,25(OH)2D3 failed to prevent prednisolone osteopenia because of its tendency to increase bone resorption.
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    Epilepsy and electromagnetic fields: effects of simulated atmospherics and 100-Hz magnetic fields on audiogenic seizure in rats (1988)
    Springer
    International journal of biometeorology 32 (1988), S. 17-20 
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    ISSN: 1432-1254
    Keywords: Epilepsy ; Electromagnetic fields ; Rat ; Audiogenic seizure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P〈0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.
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    Demonstration of correlations between the 8 and 10 kHz atmospherics and the inflammatory reaction of rats after carrageenan injection (1988)
    Springer
    International journal of biometeorology 32 (1988), S. 201-204 
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    ISSN: 1432-1254
    Keywords: Atmospherics ; Carrageenan inflammation ; Rat ; Susceptibility ; Correlations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient (r) of 0.30; there is a negative coefficient of −0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics (r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day:r=0.49 for the 8 kHz atmospherics (P〈0.02) andr=0.44 for the 10 kHz atmospherics (P〈0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multipleR=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz,P〈0.05).
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    Localization of phytohemagglutinin in the embryonic axis of Phaseolus vulgaris with ultra-thin cryosections embedded in plastic after indirect immunolabeling (1984)
    Springer
    Planta 162 (1984), S. 548-555 
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    ISSN: 1432-2048
    Keywords: Immunocytochemistry ; Lectin (localization) ; Phaseolus (lectin) ; Phytohemagglutinin ; Seed (lectin)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have examined the properties and subcellular localization of phytohemagglutinin (PHA), the major lectin of the common bean (Phaseolus vulgaris.), in the axis cells of nearly mature and imbibed mature seeds. On a protein basis the axis contained about 15% as much PHA as the cotyledons. Localization of PHA was done with an indirect immunolabeling method (rabbit antibodies against PHA, followed by colloidal gold particles coated with goat antibodies against rabbit immunoglobulins) on ultra-thin cryosections which were embedded in plastic on the grids after the immunolabeling procedure. The embedding greatly improved the visualization of the subcellular structures. The small (4 nm) collodial gold particles, localized with the electron microscope, were found exclusively over small vacuoles or protein bodies in all the cell types examined (cortical parenchyma cells, vascular-bundle cells, epidermal cells). The matrix of these vacuoles-protein bodies appears considerably less dense than that of the protein bodies in the cotyledons, but the results confirm that in all parts of the embryo PHA is localized in similar structures.
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    Immunochemical studies on xanthine dehydrogenase of soybean root nodules (1986)
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    Planta 167 (1986), S. 190-195 
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    ISSN: 1432-2048
    Keywords: Glycine (xanthine dehydrogenase) ; Immunocytochemistry ; Polyclonal antibody ; Root nodule ; Xanthine dehydrogenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Xanthine dehydrogenase (XDH, EC 1.2.1.37) was purified from root nodules of soybean (Glycine max) and used to prepare a polyclonal rabbit antiserum. Monospecificity of this antiserum was ascertained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipate. During root nodule development of soybean, only one form of XDH was detected on an immunological basis. Titration of XDH by immunoelectrophoresis showed that a remarkable increase in the amount of XDH occurred between two and four weeks after inoculation, in parallel with the increase in enzyme activity. Localization of XDH by immunofluorescence indicated that the enzyme was present exclusively in uninfected cells where it appeared to be associated with discrete organellels
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    Immunocytochemical localization of reserve protein in the endoplasmic reticulum of developing bean (Phaseolus vulgaris) cotyledons (1980)
    Springer
    Planta 150 (1980), S. 419-425 
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    ISSN: 1432-2048
    Keywords: Cotyledons ; Endoplasmic reticulum ; Ferritin labeling ; Immunocytochemistry ; Phaseolus ; Protein (reserve) ; Reserve protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The ultrastructure of the storage parenchyma cells of the cotyledons of developing bean (Phaseolus vulgaris L.) seeds was examined in ultrathin frozen sections of specimens fixed in a mixture of glutaraldehyde, formaldehyde and acrolein, infused with 1 M sucrose, and sectioned at-80° C. Ultrastructural preservation was excellent and the various subcellular organelles could readily be identified in sections which had been stained with uranyl acetate and embedded in Carbowax and methylcellulose. The cells contained large protein bodies, numerous long endoplasmic reticulum cisternae, mitochondria, dictyosomes, and electron-dense vesicles ranging in size from 0.2 to 1.0 μm. Indirect immunolabelling using rabbit immunoglobulin G against purified phaseolin (7S reserve protein), and ferritin-conjugated goat immunoglobulin G against rabbit immunoglobulin G was used to localize phaseolin. With a concentration of 0.1 mg/ml of anti-phaseolin immunoglobin G, heavy labeling with ferritin particles was observed ober the protein bodies, the cisternae of the endoplasmic reticulum, and the vesicles. The same structures were lightly labeled when the concentration of the primary antigen was 0.02 mg/ml. Ferritin particles were also found over the Golgi bodies. The absence of ferritin particles from other organelles such as mitochondria and from areas of cytoplasm devoid of organelles indicated the specificity of the staining, especially at the lower concentration of anti-phaseolin immunoglobulin G.
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    On the cellular localization of phosphoenolpyruvate carboxylase in Sorghum leaves (1981)
    Springer
    Planta 151 (1981), S. 226-231 
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    ISSN: 1432-2048
    Keywords: Immunocytochemistry ; (PEP carboxylase) ; PEP carboxylase ; Sorghum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The localization of phosphoenol pyruvate carboxylase (EC 4.1.1.3.1.) in the leaf cells of Sorghum vulgare was investigated by using three techniques: the conventional aqueous and non aqueous methods gave conflicting results; the immunocytochemical techniques clearly showed that the enzyme is predominantly located in the cytoplasm of mesophyll cells.
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    The effects of long term administration of dopamine on renal function in hypertensive patients (1973)
    Springer
    European journal of clinical pharmacology 6 (1973), S. 150-155 
    Details
    ISSN: 1432-1041
    Keywords: Dopamine ; renal blood flow ; hypertension ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of an intravenous infusion of dopamine (0.5 to 1.25 µg/kg/min) for periods of between 36 and 105h has been studied in eight patients with hypertension and varying degrees of renal impairment. There was a significant rise in the glomerular filtration rate (GFR) from 31.2±20.2 to 42.8±26.8 ml/min (p〈.05) after four hours of the infusion but after 48 h of infusion the mean GFR was no different from the control value. The paraaminohippuric acid (PAH) clearance also rose from 129.8±115.4 ml/min to 173.1±164.3 ml/min (p〈0.05) after four hours of infusion, but like the GFR it was no different from control after 48 h of the infusion. The daily urine volumes increased significantly during the dopamine infusion from 2176.0±49.2 ml/day to 3809.0±118.8 ml/day (p〈0.002) but had returned to control values after 48 h of continuing dopamine infusion. Following the end of the infusion there was a significant reduction in the urine volume to 1213.0±195.0 ml/day (p〈0.001). There was a rise in sodium excretion during the dopamine infusion from 94.8±50.7 meq/day to 264.7±172.8 meq/day (p〈0.01) with a fall after the end of the infusion to 33.2±27.5 meq/day (p〈0.05). There was no change in the blood urea during the dopamine infusion but after stopping the infusion the blood urea rose from 83.5±39.4 mg% to 95.1±39.0 mg% (p〈0.02). We conclude that intravenous infusion of dopamine to patients with hypertension and renal impairment may produce initial clinical improvement but is of little therapeutic benefit when given for prolonged periods.
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  • 43
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    Treatment of hypertension with a new beta-blocking agent, pindolol (Visken®) (1973)
    Springer
    European journal of clinical pharmacology 6 (1973), S. 217-219 
    Details
    ISSN: 1432-1041
    Keywords: Beta-blockade ; substituted indoles ; hypertension ; heart rate ; clinical trial ; pindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Forty patients with essential hypertension were treated with a new beta-blocking agent, 4-2 (2-hydroxy-3-isopropyl-amino-propoxy)-indole, pindolol (Viskén®). Pindolol caused a significantly greater reduction of blood pressure in most of the patients than a placebo and the effects persisted for some time after its withdrawal. There were few side effects. Its mode of action and a safe dosage regime are discussed.
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  • 44
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    Potassium deficiency in hypertensives treated with diuretics. Analysis of three alternative treatments by an oral test for potassium deficiency (1974)
    Springer
    European journal of clinical pharmacology 7 (1974), S. 401-405 
    Details
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; spironolactone ; hypertension ; potassium deficiency ; diuretic ; Kühns' test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Kühns' oral test for potassium deficiency (KDT) has been used to evaluate potassium balance after treatment with diuretics. The test was first standardised in 23 patients, both with and without known potassium deficiency. Subsequently, 18 patients with essential hypertension were investigated before and after the use of 3 different diuretics, each for a period of 6 weeks; all patients received all three forms of treatment but in different sequence. Before treatment the patients excreted an average of 121 mEq potassium a day in urine after oral administration of potassium 127 mEq (citrate). After treatment with chlorthalidone (Hygroton®), 50 mg a day, the excretion of potassium decreased significantly to 83 mEq, suggesting an intracellular deficit of it. Treatment with chlorthalidone 50 mg and potassium chloride 2 g daily (Hygroton — K®), led to potassium excretion of 100 mEq after loading, which was distinctly, but not significantly, larger than in the period of treatment with chlorthalidone alone. After chlorthalidone 50 mg daily and spironolactone (Aldactone “Searle”®), 25 mg q. i. d., the excretion of potassium was 121 mEq, which was the same as before treatment. The mean serum potassium before treatment was 4.4 mEq/l, after chlorthalidone 3.8 mEq/l, after chlorthalidone plus potassium chloride 3.9 mEq/l, after chlorthalidone combined with spironolactone 3.9 mEq/l. The results were in agreement with previously published investigations of “exchangeable potassium” after similar treatments. As the test for potassium deficiency gave better information about the amount of intracellular potassium in the body than analysis of serum potassium, it is suitable for the evaluation of potassium deficiency associated with diuretic therapy.
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  • 45
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    Effect of methyldopa on prolactin serum concentration (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 513-515 
    Details
    ISSN: 1432-1041
    Keywords: methyldopa ; prolactin ; hypertension ; sustained release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.
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  • 46
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    Evaluation of two oxprenolol oral osmotic (OROS) delivery systems in patients with essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 605-611 
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    ISSN: 1432-1041
    Keywords: oxprenolol ; hypertension ; osmotic delivery system ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS. At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses. However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade. The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration. These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.
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    URL: http://dx.doi.org/10.1007/BF00615225
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  • 47
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    Comparison of concomitant nicardipine hydrochloride and propranolol with propranolol alone in patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 21-25 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; propranolol ; hypertension ; concomitant administration ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A twelve-week parallel study was conducted to compare the efficacy and safety of nicardipine plus propranolol with that of propranolol alone in 67 patients with mild to moderate essential hypertension. Efficacy data was analysed for 50 patients. The regimens used were 90 mg · day−1 of nicardipine and 120 mg · day−1 of propranolol. Both treatments significantly reduced supine and standing systolic and diastolic blood pressure from baseline values at all visits. At all visits, concomitant administration of nicardipine and propranolol produced a greater reduction in systolic and diastolic pressures than did propranolol alone, although the difference between treatments did not always reach statistical significance. Few adverse events were reported, and none was clinically important. We conclude that nicardipine taken concomitantly with propranolol is more effective than propranolol alone in treating patients with hypertension and that the combined regimen is well tolerated.
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  • 48
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    The pharmacokinetics of ketanserin after a single dose and at steady-state in hypertensive subjects (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 423-426 
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    ISSN: 1432-1041
    Keywords: Ketanserin ; pharmacokinetics ; hypertension ; ketanserinol ; predicted plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of ketanserin in 6 hypertensive patients after a single oral 40 mg dose and at steady-state after 4 weeks treatment with 20 mg and then 40 mg 12-hourly. Pharmacokinetic variables after a single dose were similar to those reported in healthy volunteers, with median values for Cmax 112 ng·ml−1, tmax 1 h, and t1/2 19 h. The corresponding values for the metabolite ketanserinol were Cmax 155 ng·ml−1, tmax 2 h, and t1/2 25 h. The median AUC was 3.3 times greater for ketanserinol than for the parent drug. These results were used to predict the mean steady-state plasma concentrations of ketanserin and ketanserinol. Predicted values were on average similar to those observed after four weeks treatment with 40 mg 12-hourly, although there were marked differences between the observed and predicted values in some patients. There was no evidence of time- or dose-dependent kinetics for ketanserin, but the study had insufficient power to exclude the occurrence of these phenomena entirely.
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  • 49
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    Efficacy and tolerability of a new controlled-release formulation of metoprolol: A comparison with conventional metoprolol tablets in mild to moderate hypertension (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S39 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; controlled-release metoprolol ; systolic and diastolic blood pressure ; heart rate ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained ≥95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure 〈95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.
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  • 50
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    A comparison of felodipine and propranolol as additions to hydrochlorothiazide in the treatment of hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 115-118 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; propranolol ; hydrochlorothiazide ; hypertension ; general practice ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]≧95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not ≦90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients. Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP ≦ 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm). In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.
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  • 51
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    Haemodynamic effects of short-term treatment with bopindolol in essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 411-413 
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    ISSN: 1432-1041
    Keywords: bopindolol ; hypertension ; beta-adrenoceptor blocker ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients (mean age 53 years) with essential hypertension have been studied at rest and during exercise following oral treatment for 6 weeks with a new beta-adrenoceptor blocking agent, bopindolol. The treatment caused a significant decrease in systolic and diastolic arterial blood pressure and heart rate, both at rest and during exercise. Stroke volume fell, too, and therefore so did cardiac output, whereas the systemic vascular resistance was increased. Left ventricular filling pressure was elevated both at rest and during exercise following bopindolol therapy. However, a different haemodynamic pattern was noted in patients with elevated total peripheral resistance prior to therapy (Group 1) compared to patients with normal or subnormal peripheral resistance (Group 2). A decrease in systemic vascular resistance seemed to be the cause of the fall in blood pressure in Group 1, as the expected increase in vascular resistance did not occur, whereas a reduction in cardiac output was of greater importance in Group 2. During exercise the lowering of arterial blood pressure in both groups was mediated by a reduction in cardiac output.
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    The efficacy and tolerability of atenolol, nifedipine, and their combination in the management of hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 543-548 
    Details
    ISSN: 1432-1041
    Keywords: atenolol ; nifedipine ; hypertension ; adverse effects ; fixed combination ; drug efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this randomized, double-blind, crossover study we investigated the haemodynamic effects of a beta-blocker (atenolol 50 mg) and a calcium antagonist (nifedipine SR 20 mg) given either separately or in combination in three groups of hypertensive patients. Each treatment was administered twice daily. The fixed combination given twice daily for four weeks produced reductions in blood pressure which lasted for at least 12 h after administration of the last dose. The control of blood pressure by the combination was superior to that achieved by its individual components. Adverse effects normally associated with nifedipine were less frequent when it was given with atenolol. Compliance with treatment was good, but best when the drugs were given together rather than separately. A fixed combination of atenolol and nifedipine may prove useful in treating hypertensive patients inadequately controlled on beta-blocker therapy alone.
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  • 53
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    Doxazosin in patients with hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 21-24 
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    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
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  • 54
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    The effect of hydralazine on steady-state plasma concentrations of metoprolol in pregnant hypertensive women (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 131-135 
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    ISSN: 1432-1041
    Keywords: metoprolol ; hydralazine ; hypertension ; pregnancy ; pharmacokinetics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the plasma concentrations levels of metoprolol after its twice daily administration in a dose of 50 mg for 4 days in ten, hypertensive pregnant women to the during monotherapy and in combination with 25 mg of hydralazine given twice daily. Hydralazine increased the median AUC and Cmax of metoprolol by 38% and 88% respectively, and decreased the tmax from 1.5 h to 1.0 h. Hydralazine had no effect on the plasma concentrations of alpha-OH-metoprolol. These results suggest that the effect of hydralazine on metoprolol plasma concentrations is primarily due to a reduction in first-pass elimination.
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    A possible drug interaction between rifampicin and enalapril (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 431-432 
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    ISSN: 1432-1041
    Keywords: rifampicin ; enalapril ; hypertension ; drug interaction ; case report
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary When a 35-year-old man with essential hypertension was treated with antibiotics for brucellosis his blood pressure rose significantly. While all other treatment was kept constant rifampicin was discontinued. On rechallenge rifampicin did not alter serum concentrations of enalapril or the area under the curve (AUC) between 0 and 7 h, but it did reduce the AUC of the active metabolite enalaprilat by 31%. These observations suggest that there may be an interaction between rifampicin and enalapril, causing reduced hypotensive efficacy of enalapril. The mechanism of such an interaction merits further study, but it could be due to enhanced renal clearance of enalaprilat.
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  • 56
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    Comparison of nicardipine and propranolol in the treatment of mild and moderate hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 119-126 
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    ISSN: 1432-1041
    Keywords: hypertension ; nicardipine ; propranolol ; serum lipids ; electrocardiogram ; side-effects ; ECG changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind controlled trial 22 patients with mild or moderate essential hypertension were treated with nicardipine 30 mg t.d.s. and 19 patients with propranolol 80 mg t.d.s. as monotherapy for 24 weeks. Blood pressure in both groups at the end of trial was equally and significantly reduced; systolic pressure 22.2 mmHg and diastolic pressure 15.5 mmHg in the supine position, and 24.4 mmHg and 18.4 mmHg, respectively, in the standing position in those on nicardipine, and by 23.7 and 16.2 mmHg and 28.0 and 19.2 mmHg, respectively, in the propranolol group. There was an initial increase in heart rate in the nicardipine group, but the rise was only moderate (3 beats/min supine p=0.3219, and 7 beats/min standing, p=0.0203) at the end of the 24 weeks. In the propranolol group heart rate was reduced markedly. Adverse effects occurred in 77% of patients on nicardipine and in 63% of those on propranolol, and there were no unexpected findings. The effects were mild in both groups and did not lead any patient to stop medication. One patient on propranolol was withdrawn from the trial because of poor blood pressure control and suspected angina pectoris after 5 weeks on active medication. There were no significant changes in blood chemistry, including lipoprotein classes. Overall, in comparison with propranolol, nicardipine was effective, well-tolerated and safe to use in the monotherapy of mild or moderate essential hypertension.
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    Metabolic effects of long-term therapy with muzolimine and chlorthalidone in hypertension (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 515-517 
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    ISSN: 1432-1041
    Keywords: muzolimine ; chlorthalidone ; hypertension ; serum electrolytes ; potassium ; ion transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous short-term studies of muzolimine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthalidone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentrations remained unchanged, while a significant fall in potassium occured with chlorthalidone. Neither drug affected the activity of sodium-potassium cotransport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial pressure and on the other metabolic variables tested.
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  • 58
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    Sustained release verapamil in renal hypertension (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. 549-555 
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    ISSN: 1432-1041
    Keywords: verapamil ; sustained release formulation ; hypertension ; renal disease ; kidney function ; angiotensin II ; aldosterone ; arginine vasopressin ; atrial natriuretic peptide ; lipids and lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r=−0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.
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  • 59
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    A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; hydrochlorothiazide ; hypertension ; blood pressure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained ≥95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective ‘calcium antagonist’ felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metroprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if ‘control’ of BP (dBP 〈90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.
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    Pharmacokinetics of lisinopril in hypertensive patients with normal and impaired renal function (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 61-65 
    Details
    ISSN: 1432-1041
    Keywords: lisinopril ; renal failure ; half-life ; drug dose ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function. In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h. It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.
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    URL: http://dx.doi.org/10.1007/BF01061419
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    A double-blind and cross-over comparison of once daily doxazosin and placebo with steady-state pharmacokinetics in elderly hypertensive patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 119-123 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
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    URL: http://dx.doi.org/10.1007/BF00614546
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    Cadralazine pharmacokinetics — A pilot study (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 571-572 
    Details
    ISSN: 1432-1041
    Keywords: cadralazine ; pharmacokinetics ; 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/BF00558256
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    Ketanserin combined with a beta-blocker or diuretic in essential hypertension. A multicentre study (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 573-577 
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    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; combination therapy ; diuretic ; beta-adrenergic blocker ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination. The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mm Hg to 156/91 mm Hg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats·min−1 was observed with the ketanserin + β-blocker combination. The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mm Hg to 146/92 mm Hg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups. There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination. The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.
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    URL: http://dx.doi.org/10.1007/BF00637591
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    Effect of controlled-release metoprolol on blood pressure and exercise heart rate in hypertension: A comparison with conventional tablets (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S33 
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    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; tolerability ; exercise ; once-daily dosing ; controlled-release formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind study with parallel groups a new controlled-release (CR) formulation of metoprolol1, 100 mg once daily, was compared with conventional metoprolol tablets, 100 mg once daily, in 27 patients with primary hypertension. Exercise tests on a bicycle ergometer were undertaken 24 h after intake of the last dose of the drug following a four-week placebo run-in period and after four weeks of active treatment. Heart rate, measured in the supine position and during exercise at the highest comparable workload, was reduced significantly more by metoprolol CR (p〈0.05), thus indicating a higher degree of β1-blockade at the end of the dose interval with metoprolol CR. There was a greater reduction in supine systolic pressure (p〈0.05) but not in supine diastolic pressure after metoprolol CR than after conventional tablets at 24 h. There was no significant difference between the two groups with respect to reduction in systolic blood pressure during exercise. The 24-h plasma concentrations of metoprolol CR and conventional tablets correlated with the effects on heart rate, but not with blood pressure. The tolerability of metoprolol CR was comparable with that of metoprolol administered as conventional tablets. In conclusion, there was significantly greater β1-blockade 24 h after the intake of drug after metoprolol CR compared with conventional tablets.
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    URL: http://dx.doi.org/10.1007/BF00578410
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    Comparison of the antihypertensive effects of celiprolol and acebutolol (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 125-128 
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    ISSN: 1432-1041
    Keywords: celiprolol ; acebutolol ; hypertension ; beta-blockers ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the new cardioselective beta-blocker celiprolol and acebutolol have been compared. Thirty patients with arterial hypertension WHO Grade I–II were treated in a double-blind fashion with celiprolol or acebutolol. Before starting the treatment and on Days 15 and 29, before the morning dose, blood samples were taken for measurement of the plasma level of celiprolol. At the same times physical examinations, and clinical and urine chemistry analyses were performed. At the 99% probability level both drugs had significantly lowered the systolic and diastolic blood pressures to normal values at the end of the second and fourth weeks. There was no significant difference between their antihypertensive efficacy. The decrease in diastolic blood pressure at the end of the second week was significantly correlated with the reciprocal of the plasma celiprolol concentration at steady-state at the end of the dosage interval.
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    URL: http://dx.doi.org/10.1007/BF00614547
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    Effects of dilevalol, an R, R-isomer of labetalol, on blood pressure and renal function in patients with mild-to-moderate essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 9-15 
    Details
    ISSN: 1432-1041
    Keywords: dilevalol ; hypertension ; labetolol R-R-isomer ; renal function ; plasma renin activity ; plasma aldosterone ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new β-adrenoceptor blocker with β2-receptor stimulating and α-recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks. Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study. Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA. The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.
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    URL: http://dx.doi.org/10.1007/BF00555500
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    Dose-titration study of alfuzosin, a new alpha1-adrenoceptor blocker, in essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 25-30 
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    ISSN: 1432-1041
    Keywords: alfuzosin ; alpha1-adrenoceptor blockers ; hypertension ; adverse reactions ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week runin placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was 〉90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypothensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml. Nine of the 11 patients reached the end-point (supine diastolic BP≤90 mm Hg) at the end of 28 days: 1 at the dose of 5 mg b.d., 6 at 10 mg b.d. and 2 at 20 mg q.i.d. At the high dose they both complained of palpitations. Two other patients complained of mild and transient palpitations at lower doses.
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    Effect of clonidine on beta-endorphin, ACTH and cortisol secretion in essential hypertension and obesity (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 115-121 
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    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; obesity ; betaendorphin ; ACTH ; cortisol ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of alpha2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00609239
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    The effects of the 5 HT2 antagonist ritanserin on blood pressure and serotonin-induced platelet aggregation in patients with untreated essential hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 123-129 
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    ISSN: 1432-1041
    Keywords: ritanserin ; hypertension ; serotonin ; (5 HT) ; blood pressure ; platelet aggregation ; QT interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have given the selective 5 HT2 antagonist ritanserin in a dose of 10 mg twice daily for 4 weeks in a double-blind, randomized, placebocontrolled, parallel group study of 18 patients with untreated essential hypertension. The fall in single platelet count due to 5 HT-induced platelet aggregation was significantly reduced by ritanserin compared with placebo (p〈0.05). There were no significant changes in supine or erect blood pressure or heart rate after ritanserin compared to placebo. Forearm blood flow, measured by mercury-in-strain gauge venous occlusion plethysmography, was not significantly altered by ritanserin. Ritanserin caused prolongation of the QTc interval by 41 (SEM 11) ms (p〈0.05 compared to placebo) but had no detectable effect on QRS duration, features suggestive of Class III antiarrhythmic activity. These findings do not support an independent role of the 5 HT2 receptor in maintaining raised arterial pressure in essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00609240
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    Inhibition of the aldosterone response to sodium depletion in man by stimulation of dopamine DA2 receptors (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 323-326 
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    ISSN: 1432-1041
    Keywords: aldosterone ; DA2-receptor ; co-dergocrine ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. The PAC response to sodium depletion was reduced to 155 (29) pg/ml by co-dergocrine. No significant PAC changes were found in patients maintained on a normal sodium intake. In addition the drug did not significantly modify plasma renin activity (PRA) in either experimental group. These results suggest that the dopaminergic inhibition of aldosterone secretion in man is mediated by DA2-receptors in the adrenal cortex.
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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 
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    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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    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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    Rapid control of hypertension with oral bethanidine (1972)
    Springer
    European journal of clinical pharmacology 4 (1972), S. 217-221 
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    ISSN: 1432-1041
    Keywords: Bethanidine ; guanethidine ; hypertension ; adrenergic blockade ; blood pressure ; dose response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dosing schedule for the administration of oral bethanidine is described, which achieved optimal cumulative effect in each of 8 patients in 3 days or less. Individual patient dosage titration is necessary, because the required cumulative dose cannot be predicted on the basis of blood pressure, or creatinine clearance. The time course of the blood pressure response after the peak acute hypotensive effect was found to be variable and dependent upon the magnitude of effect and time of day. No blood pressure effect was noted in the recumbent position.
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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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    Pharmacokinetics of verapamil in patients with hypertension (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 155-163 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; verapamil ; norverapamil ; pharmacokinetics ; dosing frequency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve hypertensive patients (WHO Stage I-II) were given oral verapamil (Isoptin) b.d. or t.d.s. as long-term treatment. The pharmacokinetics of verapamil and norverapamil were studied both after single and b.d. and t.d.s. doses of verapamil 240, 360 or 480 mg daily adjusted according to the blood pressure response. The apparent oral clearance of verapamil was decreased after both the twice and thrice daily dosage regimens (1.38 and 1.841/min, respectively) as compared to the single dose (4.39 l/min). The plasma half-life of verapamil was increased from 3.34 h (single dose) to 4.65 h (b.i.d.). Decreased elimination of norverapamil was also found after multiple doses of verapamil, as shown by an increase in the adjusted AUC of norverapamil (adjusted to a verapamil dose of 80 mg), namely from 574.9 h·ng·ml−1 (single dose) to 1172 h·ng·ml−1 (b.d.) and to 841 h·ng·ml−1 (t.d.s.). The plasma half-life of norverapamil increase from 5.68 h to 7.34 h during twice daily dosing. During thrice daily verapamil, no increase in plasma half-life was found either for verapamil or norverapamil, probably due to the relatively short sampling time (6 h). The plasma concentration of verapamil and the reduction in supine systolic and diastolic blood pressure were correlated. The mean decrease in supine systolic blood pressure was 5.8 mm Hg per 100 ng verapamil/ml plasma, and for diastolic pressure 2.9 mm Hg per 100 ng verapamil/ml plasma. The mean steadystate plasma concentrations of verapamil were similar after twice and thrice daily dosing regimens, which agrees with the clinical observation that blood pressure control in hypertensive patients is as good after verapamil b.d. and t.d.s.
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    Hypertensive emergencies treated with oral clonidine (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 227-229 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; hypotensive therapy ; hypertensive emergency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-eight severely hypertensive patients were treated with oral clonidine. Each patient received a “loading” dose of 0.2 mg clonidine, followed by 0.1 mg hourly until the blood pressure was substantially reduced, or until a total dose of 0.8 mg has been administered. Thirty-five (82.1%) patients responded favourably, with a reduction in the systolic blood pressure in the supine position from 210±20 to 145±20 and to 98±15 mmHg diastolic after 6 hours. The average dose of clonidine was 0.5 mg. Side-effects were minimal. The study has shown that oral clonidine given in a “loading” dose is safe and effective in the management of patients with hypertensive emergencies, and it may have an advantage over other antihypertensive drugs administered parenterally.
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    Pharmacokinetics of sotalol after chronic administration to patients with renal insufficiency (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
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    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
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    Withdrawal of guanfacine after long-term treatment in essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 19-24 
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    ISSN: 1432-1041
    Keywords: hypertension ; guanfacine ; central antihypertensives ; withdrawal ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Guanfacine (2–6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2–4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2–3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.
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    Maximal exercise power after a single dose of metoprolol and of slow-release metoprolol (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 225-229 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; slow-release preparations ; maximal exercise power ; fatigue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The treatment of hypertension with a single daily-dose of a beta-blocker gives rise to high peak-plasma concentrations 1.5 h after ingestion. After slow release-preparations of beta-blockers, the peak concentrations are half those produced by the conventional preparation at the same oral dose. A frequently occurring side-effect of beta-blocker therapy is fatigue. In this study the effect of a single dose of metoprolol 300 mg, 200 mg, 200 mg slow-release and a placebo on maximal exercise power was tested in 6 healthy subjects, 1.5 h and 24 h after ingestion. Maximal exercise power was significantly reduced 1.5 h after ingestion of metoprolol 300 mg and 200 mg. No change was found 1.5 h after 200 mg of a slow-release preparation. The possible reasons for reduced maximal exercise power are discussed. It is concluded that use of a beta-blocker for the treatment of hypertension in a single daily-dose regimen may be a reason to prefer a slow-release preparation.
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    URL: http://dx.doi.org/10.1007/BF00563003
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    Monoamine metabolites in cerebrospinal fluid during treatment of hypertension with prazosin (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 399-401 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six hypertensive patients were treated with prazosin up to a final dose of 3–4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.
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    URL: http://dx.doi.org/10.1007/BF00636792
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    Renin-angiotensin-aldosterone system (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 105-108 
    Details
    ISSN: 1432-1041
    Keywords: renin ; angiotensin ; aldosterone ; hypertension ; hypoaldosteronism ; pseudohypoaldosteronism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is increased activity of the renin, angiotensin, aldosterone (RAA) system in infancy and childhood. An inverse relationship between plasma renin, aldosterone and age has been demonstrated. In childhood hypertension due to renovascular disease or pyelonephritic scarring peripheral plasma renin is increased. Renal vein renin measurements in children with renal hypertension have proved valuable in predicting surgical curability of the underlying lesion. The upper limit of normal for the renal venous renin ratio in normotensive children without renal disease is 1.5. Pharmacological blockade of the RAA system has a place in diagnosis and treatment of hypertensive children. The plasma renin aldosterone profile is diagnostically useful in the investigation of salt-wasting disease and can easily distinguish between aldosterone biosynthetic defects and pseudohypoaldosteronism.
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    URL: http://dx.doi.org/10.1007/BF00561486
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    Comparison of the effects of propranolol and labetalol on renal haemodynamics at rest and during exercise in essential hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 135-139 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.
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    URL: http://dx.doi.org/10.1007/BF00561580
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    Double-blind controlled trial of molsidomine in hypertension (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 231-235 
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    ISSN: 1432-1041
    Keywords: molsidomine ; hypertension ; hypotension ; angina pectoris
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Molsidomine (M), a new long-lasting antianginal compound, was studied in 38 hypertensive patients to assess its antihypertensive properties. Six patients were selected for an acute, single dose comparative trial with placebo over 8 h after treatment. The remaining 32 patients were used in a 1 month trial to study the effect on BP of more prolonged treatment. Systolic, diastolic and mean BP were significantly reduced after a single dose of M 4 mg, and the effect lasted for about 8 h. M also inhibited the hypertensive response to isometric exercise in handgrip tests performed 1 and 8 h after M ingestion. A dose-related decrease in systolic and diastolic BP in the one month trial was also observed. In addition to its antianginal properties, M appears to possess an interesting effect on BP in mildly to moderately hypertensive patients. A fall in BP is also a valuable effect in coronary patients with augmented metabolic demands of the heart.
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    URL: http://dx.doi.org/10.1007/BF00563004
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    Relationship between the antihypertensive effect and steady-state plasma concentration of nifedipine given alone or in combination with a beta-adrenoceptor blocking agent (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 287-293 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; hypotensive action ; adverse effects ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine (10–20 mg t.i.d.) given alone, or in combination with a beta-adrenoceptor blocking drug, was related to the observed plasma concentration during one dosage interval at steady-state (Pl-Nifss). The study was carried out as a within-patient comparison of treatment with nifedipine or placebo for 4 weeks. A highly significant reduction in blood pressure was obtained during monotherapy, as well as during combined treatment. The blood pressure reduction when nifedipine was added to beta-adrenoceptor blockade was of the same magnitude as that observed on nifedipine monotherapy. A considerable variation in Pl-Nifss was noted (range: 2–70 ng/ml). No significant correlation was found between the percentage reduction in blood pressure and Pl-Nifss in either of the two groups. There was a close relationship between Pl-Nifss and the concentration found 4 h after the morning dose. Side-effects were common during nifedipine monotherapy and were the reason for discontinuation of treatment in 4 of 18 patients. In contrast, none of the 9 patients on combined treatment dropped-out. In neither of the treatment groups was there any evidence for sodium retention and volume expansion during the first 4 weeks expressed as weight gain or signs of cardiac insufficiency. However, in 13 patients who continued on long-term treatment for 3–14 months, a definite need for concomitant diuretic therapy was found. The results indicate that nifedipine is effective in lowering blood pressure in patients with mild to moderate essential hypertension, either when given alone or in addition to beta-adrenoceptor blockade. It appears best tolerated as combination therapy. Long-term treatment requires addition of a diuretic. Pl-Nifss did not seem to be a major determinant of the magnitude of the hypotensive response.
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    URL: http://dx.doi.org/10.1007/BF00561384
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    Antihypertensive and renal effects of orally administered verapamil (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 375-382 
    Details
    ISSN: 1432-1041
    Keywords: calcium antagonist ; verapamil ; hypertension ; vasodilators ; plasma renin activity ; mode of action ; sodium balance ; fluid balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na+/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.
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    URL: http://dx.doi.org/10.1007/BF00636788
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    Double-blind trial comparing guanfacine and methyldopa in patients with essential hypertension (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 309-315 
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    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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    The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide in essential hypertensives (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    Details
    ISSN: 1432-1041
    Keywords: tolmesoxide ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
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    URL: http://dx.doi.org/10.1007/BF00637615
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    Comparison of labetalol and clonidine in hypertension (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 363-367 
    Details
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; dose titration ; bendrofluazide ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B (5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits until normotension was achieved, or intolerable side-effects occurred. The treatment with B and L or C was then continued in a cross-over fashion for two 6-week periods, with 3 week diuretic washouts and subsequent dose-titration periods between the treatment periods. At the end of B, the supine blood pressure (BP) was 156/101, and at the end of B + L and B + C it was 136/91 (p〈0.001) and 137/91 (p〈0.001), respectively, pooling the data from both periods. At the end of B, the standing BP was 155/115, and at the end of B + L and B + C 134/100 (p〈0.001) and 139/106 (p〈0.001), respectively. The mean daily doses required were L 476mg and C 0.335 mg. On a weight basis, labetalol had about 1/1400 of the potency of clonidine. 12 patients complained of tiredness and dry mouth on clonidine and 2 patients of unsteadiness on labetalol. Labetalol caused a psoriasiform rash on the hands in one patient and limb weakness in one patient.
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    URL: http://dx.doi.org/10.1007/BF00542319
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    Prazosin depression of baroreflex function in hypertensive man (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 7-14 
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    ISSN: 1432-1041
    Keywords: prazosin ; baroreflexes ; hypertension ; reflex tachycardia ; alpha adrenergic blockade ; dopamine-beta-hydroxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essential hypertensive men were treated with prazosin alone versus placebo, and experienced a blood pressure fall (from 114.8±3.6 down to 101.1±2.5 mm Hg,p〈0.005) unaccompanied by any change in heart rate, plasma renin activity, or several other indices of sympathetic nervous system activity (plasma dopamine-β-hydroxylase activity; urinary excretion of free catecholamines and vanillyl mandelic acid; allp〉0.1). Concomitant with the blood pressure fall, there was a significant depression of baroreflex arc sensitivity, from 11.4±2.0 ms/mmHg down to 6.6±1.9 ms/mmHg (p〈0.05), without an associated change in cardiac vagal inhibition (291.2±46.2 versus 300.3±19.2 ms,p〉0.1). Baroreflex arc sensitivity depression may in part explain the lack of reflex sympathetic outflow noted during prazosin treatment of hypertension.
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    Interaction between oxprenolol and indomethacin on blood pressure in essential hypertensive patients (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 197-201 
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    ISSN: 1432-1041
    Keywords: hypertension ; oxprenolol ; indomethacin ; drug interaction ; hypotensive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic (−10.4 mmHg,p〈0.001), diastolic (−7.4 mmHg,p〈0.001) and mean (−7.7 mmHg,p〈0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: −5.9 mmHg; diastolic: −4.0 mmHg; mean: −4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis.
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    Haemodynamic profile of captopril treatment in various forms of hypertension (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 163-168 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril 450 mg/day for 4 weeks on blood pressure, heart rate, cardiac output and extracellular fluid volume were compared in severe, often drug-resistant hypertension (n=23), mild to moderate hypertension associated with renal artery stenosis (n=10) and mild to moderate essential hypertension (n=20). Plasma renin in the three groups was 52±19, 58±17 and 20±4 µU/ml (mean ± SEM), respectively. Blood pressure fell by 18±4%, 21±2% and 18±1%. The pressure drop was mainly due to a fall in peripheral vascular resistance. Addition of the diuretic hydrochlorothiazide (25–100 mg/day) caused a further fall in resistance. Despite the vasodilator effect of captopril, reflex cardiostimulation and reactive fluid retention were not observed. In severe hypertension, captopril alone was more effective in lowering blood pressure than combined diuretic-betablocker-vasodilator therapy. Moreover, cardiac output in these patients was higher and resistance was lower after captopril than during combined treatment. Thus, captopril was capable of normalising the abnormal haemodynamic state in patients with essential hypertension, and in hypertension associated with renal artery stenosis. Despite marked differences in pre-treatment plasma renin, the effects of captopril on systemic haemodynamics were similar in all the patients.
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    Acute effects of a new vasodilator, Ro 12-4713, on blood pressure, plasma renin activity, aldosterone and catecholamine levels, and renal function in hypertensive and normal subjects (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 169-177 
    Details
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; haemodynamic effects ; renal plasma flow ; renal tubular function ; plasma renin activity ; aldosterone ; Ro 12-4713
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Selected cardiovascular and endocrine effects of the new oral vasodilator Ro 12-4713 have been evaluated in an acute single dose study. In five patients with essential hypertension, Ro 12-4713 caused a dose-dependent decrease in supine and upright blood pressure and an increase in heart rate. Initial effects occurred one to 2 h after drug ingestion and maximal effects were noted after five hours and persisted for at least 8 h. Blood pressure was normalized, and the antihypertensive and chronotropic effects persisted for 24 h after a dose of about 300 mg/1.73 m2. Plasma and urinary norepinephrine and plasma renin levels tended to be raised, whereas plasma and urinary epinephrine and plasma aldosterone did not change. Changes in supine heart rate were inversely correlated with changes in mean blood pressure (r=−0.60; P〈0.02), and positively with those in plasma norepinephrine (r=0.55; P〈0.05) and renin (r=0.62, P〈0.01); changes in supine plasma renin level were also inversely correlated with those in mean blood pressure (r=−0.65; P〈0.01), and positively with those in plasma norepinephrine (r=0.58; P〈0.05). 24 h-urinary sodium excretion was significantly (P〈0.001) decreased; it was positively correlated with mean blood pressure (r=0.51; P〈0.05) and inversely with supine plasma renin activity (r=−0.63; P〈0.01). In six normal subjects and six patients with essential hypertension, effective renal plasma flow and the renal clearance of sodium, potassium, calcium and uric acid were not significantly altered five hours after a dose of Ro 12-4713 of about 250 mg/1.73 m2; glomerular filtration rate tended to be slightly decreased, and filtration fraction was significantly (P〈0.05) reduced in the hypertensive patients. At the same time blood pressure was decreased and plasma norepinephrine (P〈0.01) and renin (ns) were slightly increased in both groups. Ro 12-4713 in a single oral dose of about 300 mg appeared to be a potent, long acting, hypotensive vasodilator.
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    Antihypertensive, saluretic and hypokalaemic effects of cyclothiazide in comparison with hydrochlorthiazide with amiloride supplement (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 495-499 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; cyclothiazide ; hydrochlorthiazide ; thiazide diuretics ; potassium-sparing diuretics ; saluretic effect ; hypokalaemia ; hyperuricaemia ; amiloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive, saluretic and hypokalaemic effects of a small dose of cyclothiazide (2.5 mg daily) were compared with those of a conventional dose of an hydrochlorthiazide-amiloride hydrochloride combination (50+5 mg daily). Both preparations were given to 13 patients with mild (WHO I) hypertension in a cross-over manner for six weeks, with an intervening wash-out phase of three weeks. The antihypertensive efficacy of cyclothiazide was well comparable to that of the hydrochlorthiazide-amiloride combination, although cyclothiazide tended to inhibit renal sodium reabsorption less than the combination. Cyclothiazide tended to cause hypokalaemia, apparently due to increased potassium loss, but with the present dosage none of the 13 patients developed marked hypokalaemia (serum potassium less than 3.3 mmol/l). Both drugs led to a comparable increase in serum urate concentration. Neither of the preparations affected creatinine or free-water clearance. The results suggest that even in relatively small doses thiazides effectively decrease blood pressure, and combining thiazides with potassium-sparing diuretics is advantageous only in patients with marked hypokalaemia and its associated risks.
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    Cadralazine (ISF 2469): Dose-related antihypertensive activity after single oral administration to patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 157-161 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
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    Increased oral clearance of metoprolol in pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 217-220 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
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    URL: http://dx.doi.org/10.1007/BF00613820
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    Changes in renal function induced by endralazine, a new antihypertensive drug (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 307-314 
    Details
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610046
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  • 97
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    Electronic Resource
    Effect of indapamide on the baroreceptor reflex in essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 579-583 
    Details
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542204
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  • 98
    Electronic Resource
    Electronic Resource
    Plasma nifedipin levels and fall in blood pressure in a 53 year old woman (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 143-144 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; plasma concentration ; blood pressure response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544032
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  • 99
    Electronic Resource
    Electronic Resource
    Sequential changes in plasma renin activity and plasma catecholamines in mildly hypertensive patients during acute, furosemide-induced body-fluid loss (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 299-302 
    Details
    ISSN: 1432-1041
    Keywords: furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037937
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  • 100
    Electronic Resource
    Electronic Resource
    Ketanserin in essential hypertension: Effects during rest and exercise (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 307-312 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037939
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