Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1995 Mar;95(3):1101–1108. doi: 10.1172/JCI117757

A functional role for endogenous atrial natriuretic peptide in a canine model of early left ventricular dysfunction.

T L Stevens 1, J C Burnett Jr 1, M Kinoshita 1, Y Matsuda 1, M M Redfield 1
PMCID: PMC441446  PMID: 7883958

Abstract

Asymptomatic or early left ventricular dysfunction in humans is characterized by increases in circulating atrial natriuretic peptide (ANP) without activation of the renin-angiotensin-aldosterone system (RAAS). We previously reported a canine model of early left ventricular dysfunction (ELVD) produced by rapid ventricular pacing and characterized by an identical neurohumoral profile and maintenance of the natriuretic response to volume expansion (VE). To test the hypothesis that elevated endogenous ANP suppresses the RAAS and maintains sodium excretion in ELVD, we assessed the effects of antagonism of ANP on cardiorenal and neurohumoral function in ELVD. Chronic ANP suppression was produced by bilateral atrial appendectomies before the production of ELVD by rapid ventricular pacing (ELVD-APPX, n = 5). This group was compared with a separate group with ELVD and intact atrial appendages (ELVD-INTACT, n = 8). ELVD-APPX was characterized by lower circulating ANP (50 +/- 11 vs. 158 +/- 37 pg/ml, P < 0.05), activation of plasma renin activity (PRA) (9.4 +/- 2.4 vs. 0.6 +/- 0.4 ng/ml per h, P < 0.05) and aldosterone (36.4 +/- 12.5 vs. 2.5 +/- 0.0 ng/dl, P < 0.05) when compared to ELVD-INTACT. In comparison to the ELVD-INTACT group, sodium excretion was decreased before and during VE in the ELVD-APPX group. Acute ANP antagonism was produced by administration of the particulate guanylate cyclase coupled natriuretic peptide receptor antagonist, HS-142-1, to seven conscious dogs with ELVD and intact atrial appendages (ELVD-INTACT). HS-142-1 decreased plasma concentrations and renal generation of the ANP second messenger, cGMP, and was associated with activation of PRA and sodium retention with enhanced tubular sodium reabsorption. These data support a significant role for elevated endogenous ANP in the maintenance of sodium excretion and regulation of the RAAS in experimental ELVD.

Full text

PDF
1101

Selected References

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

  1. 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]
  2. Burnett J. C., Jr, Kao P. C., Hu D. C., Heser D. W., Heublein D., Granger J. P., Opgenorth T. J., Reeder G. S. Atrial natriuretic peptide elevation in congestive heart failure in the human. Science. 1986 Mar 7;231(4742):1145–1147. doi: 10.1126/science.2935937. [DOI] [PubMed] [Google Scholar]
  3. Cody R. J., Covit A. B., Schaer G. L., Laragh J. H., Sealey J. E., Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest. 1986 May;77(5):1441–1452. doi: 10.1172/JCI112456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drexler H., Hirth C., Stasch H. P., Lu W., Neuser D., Just H. Vasodilatory action of endogenous atrial natriuretic factor in a rat model of chronic heart failure as determined by monoclonal ANF antibody. Circ Res. 1990 May;66(5):1371–1380. doi: 10.1161/01.res.66.5.1371. [DOI] [PubMed] [Google Scholar]
  5. FUHR J., KACZMARCZYK J., KRUTTGEN C. D. Eine einfache colorimetrische Methode zur Inulinbestimmung für Nieren-Clearance-Untersuchungen bei Stoffwechselgesunden und Diabetikern. Klin Wochenschr. 1955 Aug 1;33(29-30):729–730. doi: 10.1007/BF01473295. [DOI] [PubMed] [Google Scholar]
  6. Francis G. S., Benedict C., Johnstone D. E., Kirlin P. C., Nicklas J., Liang C. S., Kubo S. H., Rudin-Toretsky E., Yusuf S. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990 Nov;82(5):1724–1729. doi: 10.1161/01.cir.82.5.1724. [DOI] [PubMed] [Google Scholar]
  7. Gottlieb S. S., Kukin M. L., Ahern D., Packer M. Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol. 1989 Jun;13(7):1534–1539. doi: 10.1016/0735-1097(89)90344-6. [DOI] [PubMed] [Google Scholar]
  8. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  9. Hayslett J. P., Kashgarian M. A micropuncture study of the renal handling of lithium. Pflugers Arch. 1979 Jun 12;380(2):159–163. doi: 10.1007/BF00582152. [DOI] [PubMed] [Google Scholar]
  10. Imura R., Sano T., Goto J., Yamada K., Matsuda Y. Inhibition by HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist of microbial origin, of atrial natriuretic peptide-induced relaxation of isolated rabbit aorta through the blockade of guanylyl cyclase-linked receptors. Mol Pharmacol. 1992 Dec;42(6):982–990. [PubMed] [Google Scholar]
  11. Lee M. E., Miller W. L., Edwards B. S., Burnett J. C., Jr Role of endogenous atrial natriuretic factor in acute congestive heart failure. J Clin Invest. 1989 Dec;84(6):1962–1966. doi: 10.1172/JCI114385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lerman A., Gibbons R. J., Rodeheffer R. J., Bailey K. R., McKinley L. J., Heublein D. M., Burnett J. C., Jr Circulating N-terminal atrial natriuretic peptide as a marker for symptomless left-ventricular dysfunction. Lancet. 1993 May 1;341(8853):1105–1109. doi: 10.1016/0140-6736(93)93125-k. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Margulies K. B., Heublein D. M., Perrella M. A., Burnett J. C., Jr ANF-mediated renal cGMP generation in congestive heart failure. Am J Physiol. 1991 Apr;260(4 Pt 2):F562–F568. doi: 10.1152/ajprenal.1991.260.4.F562. [DOI] [PubMed] [Google Scholar]
  15. Margulies K. B., Hildebrand F. L., Jr, Lerman A., Perrella M. A., Burnett J. C., Jr Increased endothelin in experimental heart failure. Circulation. 1990 Dec;82(6):2226–2230. doi: 10.1161/01.cir.82.6.2226. [DOI] [PubMed] [Google Scholar]
  16. Morishita Y., Sano T., Ando K., Saitoh Y., Kase H., Yamada K., Matsuda Y. Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor. Biochem Biophys Res Commun. 1991 May 15;176(3):949–957. doi: 10.1016/0006-291x(91)90374-g. [DOI] [PubMed] [Google Scholar]
  17. Motwani J. G., Lang C. C., Allen M. J., Johnson H. F., Struthers A. D. Dose-ranging effects of candoxatril on elimination of exogenous atrial natriuretic peptide in chronic heart failure. Clin Pharmacol Ther. 1993 Dec;54(6):661–669. doi: 10.1038/clpt.1993.204. [DOI] [PubMed] [Google Scholar]
  18. Ohyama Y., Miyamoto K., Morishita Y., Matsuda Y., Saito Y., Minamino N., Kangawa K., Matsuo H. Stable expression of natriuretic peptide receptors: effects of HS-142-1, a non-peptide ANP antagonist. Biochem Biophys Res Commun. 1992 Nov 30;189(1):336–342. doi: 10.1016/0006-291x(92)91563-6. [DOI] [PubMed] [Google Scholar]
  19. Opgenorth T. J., Burnett J. C., Jr, Granger J. P., Scriven T. A. Effects of atrial natriuretic peptide on renin secretion in nonfiltering kidney. Am J Physiol. 1986 May;250(5 Pt 2):F798–F801. doi: 10.1152/ajprenal.1986.250.5.F798. [DOI] [PubMed] [Google Scholar]
  20. Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol. 1992 Jul;20(1):248–254. doi: 10.1016/0735-1097(92)90167-l. [DOI] [PubMed] [Google Scholar]
  21. Perrella M. A., Schwab T. R., O'Murchu B., Redfield M. M., Wei C. M., Edwards B. S., Burnett J. C., Jr Cardiac atrial natriuretic factor during evolution of congestive heart failure. Am J Physiol. 1992 Apr;262(4 Pt 2):H1248–H1255. doi: 10.1152/ajpheart.1992.262.4.H1248. [DOI] [PubMed] [Google Scholar]
  22. Quinones M. A., Waggoner A. D., Reduto L. A., Nelson J. G., Young J. B., Winters W. L., Jr, Ribeiro L. G., Miller R. R. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation. 1981 Oct;64(4):744–753. doi: 10.1161/01.cir.64.4.744. [DOI] [PubMed] [Google Scholar]
  23. Redfield M. M., Aarhus L. L., Wright R. S., Burnett J. C., Jr Cardiorenal and neurohumoral function in a canine model of early left ventricular dysfunction. Circulation. 1993 Jun;87(6):2016–2022. doi: 10.1161/01.cir.87.6.2016. [DOI] [PubMed] [Google Scholar]
  24. Redfield M. M., Edwards B. S., McGoon M. D., Heublein D. M., Aarhus L. L., Burnett J. C., Jr Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog. Circulation. 1989 Sep;80(3):651–657. doi: 10.1161/01.cir.80.3.651. [DOI] [PubMed] [Google Scholar]
  25. Riegger G. A., Liebau G., Holzschuh M., Witkowski D., Steilner H., Kochsiek K. Role of the renin-angiotensin system in the development of congestive heart failure in the dog as assessed by chronic converting-enzyme blockade. Am J Cardiol. 1984 Feb 1;53(4):614–618. doi: 10.1016/0002-9149(84)90040-7. [DOI] [PubMed] [Google Scholar]
  26. Sancho J., Haber E. A direct microassay for aldosterone in plasma extracts. J Clin Endocrinol Metab. 1978 Aug;47(2):391–396. doi: 10.1210/jcem-47-2-391. [DOI] [PubMed] [Google Scholar]
  27. Sano T., Imura R., Morishita Y., Matsuda Y., Yamada K. HS-142-1, a novel polysaccharide of microbial origin, specifically recognizes guanylyl cyclase-linked ANP receptor in rat glomeruli. Life Sci. 1992;51(18):1445–1451. doi: 10.1016/0024-3205(92)90539-2. [DOI] [PubMed] [Google Scholar]
  28. Sano T., Morishita Y., Matsuda Y., Yamada K. Pharmacological profile of HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist of microbial origin. I. Selective inhibition of the actions of natriuretic peptides in anesthetized rats. J Pharmacol Exp Ther. 1992 Feb;260(2):825–831. [PubMed] [Google Scholar]
  29. Showalter C. J., Zimmerman R. S., Schwab T. R., Edwards B. S., Opgenorth T. J., Burnett J. C., Jr Renal response to atrial natriuretic factor is modulated by intrarenal angiotensin II. Am J Physiol. 1988 Mar;254(3 Pt 2):R453–R456. doi: 10.1152/ajpregu.1988.254.3.R453. [DOI] [PubMed] [Google Scholar]
  30. Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
  31. Stevens T. L., Wei C. M., Aahrus L. L., Heublein D. M., Kinoshita M., Matsuda Y., Burnett J. C., Jr Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor. Hypertension. 1994 May;23(5):613–618. doi: 10.1161/01.hyp.23.5.613. [DOI] [PubMed] [Google Scholar]
  32. Takayanagi R., Inagami T., Snajdar R. M., Imada T., Tamura M., Misono K. S. Two distinct forms of receptors for atrial natriuretic factor in bovine adrenocortical cells. Purification, ligand binding, and peptide mapping. J Biol Chem. 1987 Sep 5;262(25):12104–12113. [PubMed] [Google Scholar]
  33. Thomsen K., Holstein-Rathlou N. H., Leyssac P. P. Comparison of three measures of proximal tubular reabsorption: lithium clearance, occlusion time, and micropuncture. Am J Physiol. 1981 Oct;241(4):F348–F355. doi: 10.1152/ajprenal.1981.241.4.F348. [DOI] [PubMed] [Google Scholar]
  34. Tsutamoto T., Kanamori T., Morigami N., Sugimoto Y., Yamaoka O., Kinoshita M. Possibility of downregulation of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients with chronic severe heart failure. Circulation. 1993 Jan;87(1):70–75. doi: 10.1161/01.cir.87.1.70. [DOI] [PubMed] [Google Scholar]
  35. Volpe M., Tritto C., De Luca N., Mele A. F., Lembo G., Rubattu S., Romano M., De Campora P., Enea I., Ricciardelli B. Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure. J Clin Invest. 1991 Nov;88(5):1481–1489. doi: 10.1172/JCI115458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wada A., Tsutamoto T., Matsuda Y., Kinoshita M. Cardiorenal and neurohumoral effects of endogenous atrial natriuretic peptide in dogs with severe congestive heart failure using a specific antagonist for guanylate cyclase-coupled receptors. Circulation. 1994 May;89(5):2232–2240. doi: 10.1161/01.cir.89.5.2232. [DOI] [PubMed] [Google Scholar]
  37. Winaver J., Burnett J. C., Tyce G. M., Dousa T. P. ANP inhibits Na(+)-H+ antiport in proximal tubular brush border membrane: role of dopamine. Kidney Int. 1990 Dec;38(6):1133–1140. doi: 10.1038/ki.1990.323. [DOI] [PubMed] [Google Scholar]

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

RESOURCES