Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Mar;77(3):734–742. doi: 10.1172/JCI112368

Blood levels and renal effects of atrial natriuretic peptide in normal man.

P Weidmann, L Hasler, M P Gnädinger, R E Lang, D E Uehlinger, S Shaw, W Rascher, F C Reubi
PMCID: PMC423457  PMID: 2936762

Abstract

Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important but not sole mechanism of natriuresis and diuresis induced by alpha hANP in man.

Full text

PDF
734

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atarashi K., Mulrow P. J., Franco-Saenz R., Snajdar R., Rapp J. Inhibition of aldosterone production by an atrial extract. Science. 1984 Jun 1;224(4652):992–994. doi: 10.1126/science.6326267. [DOI] [PubMed] [Google Scholar]
  2. Atlas S. A., Kleinert H. D., Camargo M. J., Januszewicz A., Sealey J. E., Laragh J. H., Schilling J. W., Lewicki J. A., Johnson L. K., Maack T. Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide. Nature. 1984 Jun 21;309(5970):717–719. doi: 10.1038/309717a0. [DOI] [PubMed] [Google Scholar]
  3. Baines A. D., DeBold A. J., Sonnenberg H. Natriuretic effect of atrial extract on isolated perfused rat kidney. Can J Physiol Pharmacol. 1983 Dec;61(12):1462–1466. doi: 10.1139/y83-208. [DOI] [PubMed] [Google Scholar]
  4. Beasley D., Malvin R. L. Atrial extracts increase glomerular filtration rate in vivo. Am J Physiol. 1985 Jan;248(1 Pt 2):F24–F30. doi: 10.1152/ajprenal.1985.248.1.F24. [DOI] [PubMed] [Google Scholar]
  5. Borenstein H. B., Cupples W. A., Sonnenberg H., Veress A. T. The effect of a natriuretic atrial extract on renal haemodynamics and urinary excretion in anaesthetized rats. J Physiol. 1983 Jan;334:133–140. doi: 10.1113/jphysiol.1983.sp014484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Briggs J. P., Steipe B., Schubert G., Schnermann J. Micropuncture studies of the renal effects of atrial natriuretic substance. Pflugers Arch. 1982 Dec;395(4):271–276. doi: 10.1007/BF00580789. [DOI] [PubMed] [Google Scholar]
  7. Burnett J. C., Jr, Granger J. P., Opgenorth T. J. Effects of synthetic atrial natriuretic factor on renal function and renin release. Am J Physiol. 1984 Nov;247(5 Pt 2):F863–F866. doi: 10.1152/ajprenal.1984.247.5.F863. [DOI] [PubMed] [Google Scholar]
  8. Camargo M. J., Kleinert H. D., Atlas S. A., Sealey J. E., Laragh J. H., Maack T. Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Am J Physiol. 1984 Apr;246(4 Pt 2):F447–F456. doi: 10.1152/ajprenal.1984.246.4.F447. [DOI] [PubMed] [Google Scholar]
  9. Currie M. G., Geller D. M., Cole B. R., Boylan J. G., YuSheng W., Holmberg S. W., Needleman P. Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria. Science. 1983 Jul 1;221(4605):71–73. doi: 10.1126/science.6857267. [DOI] [PubMed] [Google Scholar]
  10. De Bold A. J. Heart atria granularity effects of changes in water-electrolyte balance. Proc Soc Exp Biol Med. 1979 Sep;161(4):508–511. doi: 10.3181/00379727-161-40584. [DOI] [PubMed] [Google Scholar]
  11. Düsterdieck G., McElwee G. Estimation of angiotensin II concentration in human plasma by radioimmunoassay. Some applications to physiological and clinical states. Eur J Clin Invest. 1971 Nov;2(1):32–38. doi: 10.1111/j.1365-2362.1971.tb00565.x. [DOI] [PubMed] [Google Scholar]
  12. Flynn T. G., de Bold M. L., de Bold A. J. The amino acid sequence of an atrial peptide with potent diuretic and natriuretic properties. Biochem Biophys Res Commun. 1983 Dec 28;117(3):859–865. doi: 10.1016/0006-291x(83)91675-3. [DOI] [PubMed] [Google Scholar]
  13. Garcia R., Cantin M., Thibault G., Ong H., Genest J. Relationship of specific granules to the natriuretic and diuretic activity of rat atria. Experientia. 1982 Sep 15;38(9):1071–1073. doi: 10.1007/BF01955373. [DOI] [PubMed] [Google Scholar]
  14. Garcia R., Thibault G., Cantin M., Genest J. Effect of a purified atrial natriuretic factor on rat and rabbit vascular strips and vascular beds. Am J Physiol. 1984 Jul;247(1 Pt 2):R34–R39. doi: 10.1152/ajpregu.1984.247.1.R34. [DOI] [PubMed] [Google Scholar]
  15. Goodfriend T. L., Elliott M. E., Atlas S. A. Actions of synthetic atrial natriuretic factor on bovine adrenal glomerulosa. Life Sci. 1984 Oct 15;35(16):1675–1682. doi: 10.1016/0024-3205(84)90179-6. [DOI] [PubMed] [Google Scholar]
  16. Hathaway S., Solomon S. The effect of 6-hydroxydopamine on the renal responses to atrial natriuretic extract and blood volume expansion. Proc West Pharmacol Soc. 1984;27:89–93. [PubMed] [Google Scholar]
  17. Hirata Y., Tomita M., Yoshimi H., Ikeda M. Specific receptors for atrial natriuretic factor (ANF) in cultured vascular smooth muscle cells of rat aorta. Biochem Biophys Res Commun. 1984 Dec 14;125(2):562–568. doi: 10.1016/0006-291x(84)90576-x. [DOI] [PubMed] [Google Scholar]
  18. Huang C. L., Lewicki J., Johnson L. K., Cogan M. G. Renal mechanism of action of rat atrial natriuretic factor. J Clin Invest. 1985 Feb;75(2):769–773. doi: 10.1172/JCI111759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ishihara T., Aisaka K., Hattori K., Hamasaki S., Morita M., Noguchi T., Kangawa K., Matsuo H. Vasodilatory and diuretic actions of alpha-human atrial natriuretic polypeptide (alpha-hANP). Life Sci. 1985 Mar 25;36(12):1205–1215. doi: 10.1016/0024-3205(85)90239-5. [DOI] [PubMed] [Google Scholar]
  20. Ishii M., Sugimoto T., Kobayashi T., Uehara Y., Hirata Y., Matsuoka H., Ikeda T., Sugimoto T. Effects of atrial extract on blood pressure and urinary excretion of electrolytes and prostaglandin E2 in rats. Prostaglandins Leukot Med. 1984 Dec;16(3):325–332. doi: 10.1016/0262-1746(84)90189-6. [DOI] [PubMed] [Google Scholar]
  21. Jacobowitz D. M., Skofitsch G., Keiser H. R., Eskay R. L., Zamir N. Evidence for the existence of atrial natriuretic factor-containing neurons in the rat brain. Neuroendocrinology. 1985 Jan;40(1):92–94. doi: 10.1159/000124058. [DOI] [PubMed] [Google Scholar]
  22. Johannesen J., Lie M., Kiil F. Effect of glycine and glucagon on glomerular filtration and renal metabolic rates. Am J Physiol. 1977 Jul;233(1):F61–F66. doi: 10.1152/ajprenal.1977.233.1.F61. [DOI] [PubMed] [Google Scholar]
  23. Kangawa K., Matsuo H. Purification and complete amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha-hANP). Biochem Biophys Res Commun. 1984 Jan 13;118(1):131–139. doi: 10.1016/0006-291x(84)91077-5. [DOI] [PubMed] [Google Scholar]
  24. Keeler R. Atrial natriuretic factor has a direct, prostaglandin-independent action on kidneys. Can J Physiol Pharmacol. 1982 Aug;60(8):1078–1082. doi: 10.1139/y82-155. [DOI] [PubMed] [Google Scholar]
  25. Keeler R., Azzarolo A. M. Effects of atrial natriuretic factor on renal handling of water and electrolytes in rats. Can J Physiol Pharmacol. 1983 Sep;61(9):996–1002. doi: 10.1139/y83-149. [DOI] [PubMed] [Google Scholar]
  26. Lang R. E., Thölken H., Ganten D., Luft F. C., Ruskoaho H., Unger T. Atrial natriuretic factor--a circulating hormone stimulated by volume loading. Nature. 1985 Mar 21;314(6008):264–266. doi: 10.1038/314264a0. [DOI] [PubMed] [Google Scholar]
  27. Maack T., Marion D. N., Camargo M. J., Kleinert H. D., Laragh J. H., Vaughan E. D., Jr, Atlas S. A. Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs. Am J Med. 1984 Dec;77(6):1069–1075. doi: 10.1016/0002-9343(84)90190-6. [DOI] [PubMed] [Google Scholar]
  28. Malvano R., Gandolfi C., Giannessi D., Giannotti P., Grosso P. Radioimmunoassay of aldosterone in crude plasma extracts. J Nucl Biol Med. 1976 Jan-Mar;20(1):37–44. [PubMed] [Google Scholar]
  29. Nakao K., Sugawara A., Morii N., Sakamoto M., Suda M., Soneda J., Ban T., Kihara M., Yamori Y., Shimokura M. Radioimmunoassay for alpha-human and rat atrial natriuretic polypeptide. Biochem Biophys Res Commun. 1984 Nov 14;124(3):815–821. doi: 10.1016/0006-291x(84)91030-1. [DOI] [PubMed] [Google Scholar]
  30. Napier M. A., Vandlen R. L., Albers-Schönberg G., Nutt R. F., Brady S., Lyle T., Winquist R., Faison E. P., Heinel L. A., Blaine E. H. Specific membrane receptors for atrial natriuretic factor in renal and vascular tissues. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5946–5950. doi: 10.1073/pnas.81.19.5946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nemeh M. N., Gilmore J. P. Natriuretic activity of human and monkey atria. Circ Res. 1983 Sep;53(3):420–423. doi: 10.1161/01.res.53.3.420. [DOI] [PubMed] [Google Scholar]
  32. Pollock D. M., Banks R. O. Effect of atrial extract on renal function in the rat. Clin Sci (Lond) 1983 Jul;65(1):47–55. doi: 10.1042/cs0650047. [DOI] [PubMed] [Google Scholar]
  33. Rascher W., Lang R. E., Unger T., Ganten D., Gross F. Vasopressin in brain of spontaneously hypertensive rats. Am J Physiol. 1982 Apr;242(4):H496–H499. doi: 10.1152/ajpheart.1982.242.4.H496. [DOI] [PubMed] [Google Scholar]
  34. Richards A. M., Nicholls M. G., Ikram H., Webster M. W., Yandle T. G., Espiner E. A. Renal, haemodynamic, and hormonal effects of human alpha atrial natriuretic peptide in healthy volunteers. Lancet. 1985 Mar 9;1(8428):545–549. doi: 10.1016/s0140-6736(85)91207-3. [DOI] [PubMed] [Google Scholar]
  35. Sealey J. E., Gerten-Banes J., Laragh J. H. The renin system: Variations in man measured by radioimmunoassay or bioassay. Kidney Int. 1972 Apr;1(4):240–253. doi: 10.1038/ki.1972.34. [DOI] [PubMed] [Google Scholar]
  36. Seymour A. A., Blaine E. H., Mazack E. K., Smith S. G., Stabilito I. I., Haley A. B., Napier M. A., Whinnery M. A., Nutt R. F. Renal and systemic effects of synthetic atrial natriuretic factor. Life Sci. 1985 Jan 7;36(1):33–44. doi: 10.1016/0024-3205(85)90283-8. [DOI] [PubMed] [Google Scholar]
  37. Smedes F., Kraak J. C., Poppe H. Simple and fast solvent extraction system for selective and quantitative isolation of adrenaline, noradrenaline and dopamine from plasma and urine. J Chromatogr. 1982 Aug 13;231(1):25–39. doi: 10.1016/s0378-4347(00)80506-x. [DOI] [PubMed] [Google Scholar]
  38. Sonnenberg H., Cupples W. A., de Bold A. J., Veress A. T. Intrarenal localization of the natriuretic effect of cardiac atrial extract. Can J Physiol Pharmacol. 1982 Sep;60(9):1149–1152. doi: 10.1139/y82-166. [DOI] [PubMed] [Google Scholar]
  39. Tanaka I., Misono K. S., Inagami T. Atrial natriuretic factor in rat hypothalamus, atria and plasma: determination by specific radioimmunoassay. Biochem Biophys Res Commun. 1984 Oct 30;124(2):663–668. doi: 10.1016/0006-291x(84)91606-1. [DOI] [PubMed] [Google Scholar]
  40. Tang J., Webber R. J., Chang D., Chang J. K., Kiang J., Wei E. T. Depressor and natriuretic activities of several atrial peptides. Regul Pept. 1984 Sep;9(1-2):53–59. doi: 10.1016/0167-0115(84)90007-7. [DOI] [PubMed] [Google Scholar]
  41. Thibault G., Garcia R., Cantin M., Genest J. Atrial natriuretic factor and urinary kallikrein in the rat: antagonistic factors? Can J Physiol Pharmacol. 1984 Jun;62(6):645–649. doi: 10.1139/y84-105. [DOI] [PubMed] [Google Scholar]
  42. Tremblay J., Gerzer R., Vinay P., Pang S. C., Béliveau R., Hamet P. The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase. FEBS Lett. 1985 Feb 11;181(1):17–22. doi: 10.1016/0014-5793(85)81105-4. [DOI] [PubMed] [Google Scholar]
  43. Uehlinger D. E., Weidmann P., Gnädinger M. P., Shaw S. Effects of human atrial natriuretic peptide on the pressor action of noradrenaline and angiotensin II in normal subjects. J Hypertens Suppl. 1985 Dec;3(3):S319–S321. [PubMed] [Google Scholar]
  44. Weidmann P., Beretta-Piccoli C., Link L., Bianchetti M. G., Boehringer K., Morton J. J. Cardiovascular counterregulation during sympathetic inhibition in normal subjects and patients with mild hypertension. Hypertension. 1983 Nov-Dec;5(6):873–880. doi: 10.1161/01.hyp.5.6.873. [DOI] [PubMed] [Google Scholar]
  45. Weidmann P., Beretta-Piccoli C., Ziegler W. H., Keusch G., Glück Z., Reubi F. C. Age versus urinary sodium for judging renin, aldosterone, and catecholamine levels: studies in normal subjects and patients with essential hypertension. Kidney Int. 1978 Dec;14(6):619–628. doi: 10.1038/ki.1978.171. [DOI] [PubMed] [Google Scholar]
  46. Winquist R. J., Faison E. P., Waldman S. A., Schwartz K., Murad F., Rapoport R. M. Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7661–7664. doi: 10.1073/pnas.81.23.7661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. de Bold A. J., Borenstein H. B., Veress A. T., Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981 Jan 5;28(1):89–94. doi: 10.1016/0024-3205(81)90370-2. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES