Skip to main content
Log in

Atrial natriuretic peptides: Reproducibility of renal effects and response of liver blood flow

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

To assess the variability of the response to exogenous atrial natriuretic peptide (ANP), it was infused at the rate of 1 µg/min for 2 h in 6 salt-loaded normal volunteers under controlled conditions on 2 occasions at an interval of 1 week. The effect on solute excretion and the haemodynamic and endocrine actions were highly reproducible. The constant ANP infusion caused a delayed and prolonged excretion of sodium, chloride and calcium, no change in potassium or phosphate excretion or in glomerular filtration rate but a marked decrease in renal plasma flow. Blood pressure, heart rate and the plasma levels of angiotensin II, aldosterone, arginine vasopressin and plasma renin activity were unaltered. The effect of a 2-h infusion of ANP 0.5 µg/min or its vehicle on apparent hepatic blood flow (HBF) was also studied in 14 normal volunteers by measuring the indocyanine green clearance. A 21% decrease in HBF was observed in subjects who received the ANP infusion (p<0.01 vs vehicle). Thus, ANP infused at a dose that did not lower blood pressure decreased both renal and liver blood flow in normotensive volunteers. The renal and endocrine responses to ANP were reproducible over a 1-week interval.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ackerman U, Irizawa TG, Milojevic S, Sonnenberg H (1984) Cardiovascular effects of atrial extracts in anesthetized rats. Can J Physiol Pharmacol 62: 819–826

    Google Scholar 

  • Atlas SA, Kleinert HD, Camargo MJ, Januszewicz A, Sealey JE, Laragh JH, Schilling JW, Lewicki JA, Johnson LK, Maack T (1984) Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide. Nature 309: 717–720

    Google Scholar 

  • Biollaz J, Nussberger J, Porchet M, Brunner-Ferber F, Otterbein ES, Gomez HJ, Waeber B, Brunner HR (1986) Four-hour infusions of synthetic atrial natriuretic peptide in normal volunteers. Hypertension 4 [Suppl 2]: S 101-S 108

    Google Scholar 

  • Borenstein HB, Cupples WA, Sonnenberg H, Veress AT (1983) The effects of a natriuretic atrial extract on renal hemodynamics and urinary excretion in anesthetized rat. J Physiol 334: 133–140

    Google Scholar 

  • Briggs JP, Steipe HB, Schubert G, Schnermann J (1982) Micropuncture studies of the renal effects of atrial natriuretic substance. Pflugers Arch 395: 271–276

    Google Scholar 

  • Brunner DB, Burnier M, Brunner HR (1983) Plasma vasopressin in rats: effect of sodium, angiotensin, and catecholamines. Am J Physiol 244: H259–H265

    Google Scholar 

  • Burnett JC Jr, Graujer JP, Opgenoth TS (1984) Effects of synthetic atrial natriuretic factor on renal function and renin release. Am J Physiol 247: F863–F867

    Google Scholar 

  • Bussien JP, Biollaz J, Waeber B, Nussberger J, Turini GA, Brunner HR, Brunner-Ferber F, Gomez HJ, Otterbein ES (1986) Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate and skin blood flow of normal volunteers. J Cardiovasc Pharmacol 8: 216–220

    Google Scholar 

  • Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S (1961) The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 21: 43–57

    Google Scholar 

  • Camargo MJF, Kleinert HD, Atlas SA, Sealey JE, Laragh JH, Maack T (1984) Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Am J Physiol 246: F447–F456

    Google Scholar 

  • De Bold AJ (1982) Atrial natriuretic factor of the rat heart. Proc Soc Exp Biol Med 170: 133–138

    Google Scholar 

  • De Bold AJ, Borenstein HB, Veress AT, Sonnenberg H (1981) A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 28: 89–94

    Google Scholar 

  • Feely J (1984) Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects. Br J Clin Pharmacol 17: 83–85

    Google Scholar 

  • Friedman SM, Polley JR, Friedman CL (1947) The clearance of inulin and sodium p-aminohippurate in the rat. Am J Physiol 150: 340–352

    Google Scholar 

  • Garcia R, Cantin M, Thibault G, Ong H, Genest J (1982) Relationship of specific granules to the natriuretic and diuretic activity of rat atria. Experientia 38: 1071–1073

    Google Scholar 

  • Goodfriend TL, Elliott M, Atlas SA (1984) Actions of synthetic atrial natriuretic factor on bovine adrenal glomerulosa. Life Sci 35: 1675–1682

    Google Scholar 

  • Grainger SL, Marigold JH, Keeling PWN (1982) Ranitidine and liver blood flow. Lancet 1: 398

    Google Scholar 

  • Grainger SL, Kefling PWN, Brown IMH, Marigold JH, Thompson RPH (1983) Clearance and non-invasive determination of the hepatic extraction of indocyanine green in baboons and man. Clin Sci 64: 207–212

    Google Scholar 

  • Greenway CV, Stark RD (1971) Hepatic vascular bed. Physiol Revs 51: 23–65

    Google Scholar 

  • Harrison HE (1942) A modification of the diphenylamine method for the determination of inulin. Proc Soc Exp Biol Med 49: 111–114

    Google Scholar 

  • Huang CL, Lewicki J, Johnson LK, Cogan MG (1985) Renal mechanism of action of rat atrial natriuretic factor. J Clin Invest 75: 769–773

    Google Scholar 

  • Keeler R (1982) Atrial natriuretic factor has a direct, prostaglandin-independent action on kidneys. Can J Physiol Pharmacol 60: 1078–1082

    Google Scholar 

  • Kleinert HD, Camargo MJF, Sealey JE, Laragh JH, Maack T (1982) Hemodynamic and natriuretic effects of atrial extract in the isolated perfused rat kidney. Physiologist 25: 298

    Google Scholar 

  • Maack T, Marion DN, Camargo MJF, Kleinert HD, Laragh JH, Vaughan ED Jr, Atlas SA (1984) Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the reninaldosterone system in dogs. Am J Med 77: 1069–1075

    Google Scholar 

  • Nussberger J, Fasanella d'Amore T, Porchet M, Waeber B, Brunner DB, Brunner HR, Kler L, Brown AN, Francis RJ (1986) Repeated administration of the converting enzyme inhibitor cilazapril to normal volunteers. J Cardiovasc Pharmacol (in press)

  • Nussberger J, Brunner DB, Waeber B, Brunner HR (1985) True versus immunoreactive angiotensin II in human plasma. Hypertension 7 [Suppl 1]: 1–7

    Google Scholar 

  • Nussberger J, Waeber B, Brunner HR, Burris JF, Vetter W (1984) Highly sensitive microassay for aldosterone in unextracted plasma: Comparison with two other methods. J Lab Clin Med 104 [5]: 789–796

    Google Scholar 

  • Nutt RF, Brady SF, Lyle TA, Dylion-Colton C, Palveda WJ, Ciccarone TM, Blaine EH, Winquist RJ, Bennet CD, Hirschmann R, Weber DF (1985) Synthesis of peptides with atrial natriuretic factor sequence. In: Ragnarsson V (ed) Peptides 1984. Proceedings of the 18th European Peptide Symposium. Almquist and Wiksell International, Upsala, Sweden

    Google Scholar 

  • Oshima T, Currie MG, Geller DM, Needleman P (1984) An atrial peptide is a potent renal vasodilator substance. Circ Res 54: 612–616

    Google Scholar 

  • Pegram BL, Trippodo NC, Cole FE, MacPhee AA (1984) Hypotensive effect of atrial natriuretic factor (rANF) in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Fed Proc 43: 453 (abstract 987)

    Google Scholar 

  • Pollock DM, Banks RO (1983) Effect of atrial extract on renal function in the rat. Clin Sci 65: 47–55

    Google Scholar 

  • Poulsen K, Jorgensen J (1974) An easy radioimmunological microassay of renin activity, concentration and substrate in human and animal plasma and tissues based on angiotensin I trapping by antibody. J Clin Endocrinol Metab 39: 816–825

    Google Scholar 

  • Richards AM, Nicholls MG, Ikram H, Webster RWI, Yandle TG, Espiner EA (1985) Renal, hemodynamic and hormonal effects of human alpha-atrial natriuretic peptide in healthy volunteers. Lancet 1: 545–549

    Google Scholar 

  • Seidah NG, Lazure C, Chretien M, Thibault G, Garcia R, Cantin M, Genest J, Nutt RF, Brady SF, Lyle TA, Paleveda WJ, Colton CD, Ciccarone TM, Veber DF (1984) Amino acid sequence of homologous rat atrial peptides: Natriuretic activity of native and synthetic forms. Proc Natl Acad Sci USA 81: 2640–2644

    Google Scholar 

  • Sheiner LB (1983) ELSFIT version 3.0. A program for the extended least squares fit to individual pharmacokinetic data. University of California, San Francisco, Division of Clinical Pharmacology

    Google Scholar 

  • Shepherd AN, Hayes PC, Jacyna M, Morrison L, Bouchier IAD (1985) The influence of captopril, the nitrates and propranolol on apparent liver blood flow. Br J Clin Pharmacol 19: 393–397

    Google Scholar 

  • Sonnenberg H, Cupples WA (1982) Intrarenal localization of the natriuretic effect of cardiac atrial extract. Can J Physiol Pharmacol 60: 1149–1152

    Google Scholar 

  • Svensson CK, Cumella JC, Tronolone M, Middleton E Jr, Lalka D (1985) Effects of hydralazine, nitroglycerin, and food on estimated hepatic blood flow. Clin Pharmacol Ther 37: 464–468

    Google Scholar 

  • Trippodo NC, MacPhee AA, Cole FE, Blaskesley HL (1982) Partial chemical characterization of a natriuretic substance in rat atrial heart tissue. Proc Soc Exp Biol Med 170: 502–508

    Google Scholar 

  • Trippodo NC, MacPhee AA, Cole FE (1983) Partially purified human and rat atrial natriuretic factor. Hypertension [suppl 1] 5: 181–188

    Google Scholar 

  • Vaughan ED Jr, Marion DN, Sealey JE, Camargo MJF, Kleinert HD, Maack T, Laragh JH (1983) Atrial natriuretic extract-effect on renal hemodynamics in the rabbit. Surg Forum 34: 690–692

    Google Scholar 

  • Winquist RJ, Faison EP, Nutt RF (1984) Vasodilator profile of synthetic atrial natriuretic factor. Eur J Pharmacol 102: 169–173

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biollaz, J., Waeber, B., Nussberger, J. et al. Atrial natriuretic peptides: Reproducibility of renal effects and response of liver blood flow. Eur J Clin Pharmacol 31, 1–8 (1986). https://doi.org/10.1007/BF00870977

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00870977

Key words

Navigation