Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 May;87(5):1649–1655. doi: 10.1172/JCI115180

Pulmonary and urinary clearance of atrial natriuretic factor in acute congestive heart failure in dogs.

M A Perrella 1, K B Margulies 1, C M Wei 1, L L Aarhus 1, D M Heublein 1, J C Burnett Jr 1
PMCID: PMC295256  PMID: 1850758

Abstract

Atrial natriuretic factor (ANF) is a peptide hormone of cardiac origin elevated in acute congestive heart failure (CHF), which is degraded by the enzyme neutral endopeptidase 24.11 (NEP). This study was designed to investigate the pulmonary and urinary clearance of ANF before and after the initiation of acute experimental CHF in dogs, and to assess the contribution of enzymatic degradation to these clearances in CHF. This study demonstrated a significant clearance of plasma ANF across the pulmonary circulation at baseline, and a tendency for pulmonary clearance to decrease in CHF (1115 +/- 268 to 498 +/- 173 ml/min, NS). The pulmonary extraction of ANF present at baseline was not altered with acute CHF (36.0 +/- 7.8 to 34.9 +/- 12.1%, NS). NEP inhibition (NEPI) abolished both the clearance and extraction of plasma ANF across the lung in CHF. Similarly, significant urinary clearance of ANF was present at baseline, and in acute CHF the urinary clearance of ANF decreased (0.14 +/- 0.02 to 0.02 +/- 0.01 ml/min, P less than 0.05). NEPI prevented the decrease in the urinary clearance of ANF, and enhanced the renal response to endogenous ANF, independent of further increases in plasma ANF during CHF. This study supports an important role for NEP in the pulmonary and urinary metabolism of endogenous ANF during acute CHF.

Full text

PDF
1649

Images in this article

1652Image
on p.1652
1652Image
on p.1652
1652Image
on p.1652
1652Image
on p.1652

Selected References

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

  1. Berg J. A., Hayashi M., Fujii Y., Katz A. I. Renal metabolism of atrial natriuretic peptide in the rat. Am J Physiol. 1988 Sep;255(3 Pt 2):F466–F473. doi: 10.1152/ajprenal.1988.255.3.F466. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Cavero P. G., Margulies K. B., Winaver J., Seymour A. A., Delaney N. G., Burnett J. C., Jr Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure. Circulation. 1990 Jul;82(1):196–201. doi: 10.1161/01.cir.82.1.196. [DOI] [PubMed] [Google Scholar]
  5. Condra C. L., Leidy E. A., Bunting P., Colton C. D., Nutt R. F., Rosenblatt M., Jacobs J. W. Clearance and early hydrolysis of atrial natriuretic factor in vivo. Structural analysis of cleavage sites and design of an analogue that inhibits hormone cleavage. J Clin Invest. 1988 May;81(5):1348–1354. doi: 10.1172/JCI113462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edwards B. S., Zimmerman R. S., Schwab T. R., Heublein D. M., Burnett J. C., Jr Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res. 1988 Feb;62(2):191–195. doi: 10.1161/01.res.62.2.191. [DOI] [PubMed] [Google Scholar]
  7. Erdös E. G., Skidgel R. A. Neutral endopeptidase 24.11 (enkephalinase) and related regulators of peptide hormones. FASEB J. 1989 Feb;3(2):145–151. [PubMed] [Google Scholar]
  8. 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]
  9. Hamet P., Tremblay J., Pang S. C., Skuherska R., Schiffrin E. L., Garcia R., Cantin M., Genest J., Palmour R., Ervin F. R. Cyclic GMP as mediator and biological marker of atrial natriuretic factor. J Hypertens Suppl. 1986 Jun;4(2):S49–S56. [PubMed] [Google Scholar]
  10. Hollister A. S., Rodeheffer R. J., White F. J., Potts J. R., Imada T., Inagami T. Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog. J Clin Invest. 1989 Feb;83(2):623–628. doi: 10.1172/JCI113926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Johnson A. R., Coalson J. J., Ashton J., Larumbide M., Erdös E. G. Neutral endopeptidase in serum samples from patients with adult respiratory distress syndrome. Comparison with angiotensin-converting enzyme. Am Rev Respir Dis. 1985 Dec;132(6):1262–1267. doi: 10.1164/arrd.1985.132.6.1262. [DOI] [PubMed] [Google Scholar]
  12. Kenny A. J., Stephenson S. L. Role of endopeptidase-24.11 in the inactivation of atrial natriuretic peptide. FEBS Lett. 1988 May 9;232(1):1–8. doi: 10.1016/0014-5793(88)80375-2. [DOI] [PubMed] [Google Scholar]
  13. Koepke J. P., Tyler L. D., Trapani A. J., Bovy P. R., Spear K. L., Olins G. M., Blaine E. H. Interaction of non-guanylate cyclase-linked atriopeptin receptor ligand and endopeptidase inhibitor in conscious rats. J Pharmacol Exp Ther. 1989 Apr;249(1):172–176. [PubMed] [Google Scholar]
  14. Ledsome J. R., Wilson N., Courneya C. A., Rankin A. J. Release of atrial natriuretic peptide by atrial distension. Can J Physiol Pharmacol. 1985 Jun;63(6):739–742. doi: 10.1139/y85-121. [DOI] [PubMed] [Google Scholar]
  15. Maack T., Suzuki M., Almeida F. A., Nussenzveig D., Scarborough R. M., McEnroe G. A., Lewicki J. A. Physiological role of silent receptors of atrial natriuretic factor. Science. 1987 Oct 30;238(4827):675–678. doi: 10.1126/science.2823385. [DOI] [PubMed] [Google Scholar]
  16. Margulies K. B., Cavero P. G., Seymour A. A., Delaney N. G., Burnett J. C., Jr Neutral endopeptidase inhibition potentiates the renal actions of atrial natriuretic factor. Kidney Int. 1990 Jul;38(1):67–72. doi: 10.1038/ki.1990.168. [DOI] [PubMed] [Google Scholar]
  17. Marumo F., Sakamoto H., Ando K., Ishigami T., Kawakami M. A highly sensitive radioimmunoassay of atrial natriuretic peptide (ANP) in human plasma and urine. Biochem Biophys Res Commun. 1986 May 29;137(1):231–236. doi: 10.1016/0006-291x(86)91200-3. [DOI] [PubMed] [Google Scholar]
  18. Miller W. L., Edwards B. S., Zimmerman R. S., Burnett J. C., Jr Renal-endocrine adaptations to endogenous atrial natriuretic factor during tachycardia-induced reductions in renal perfusion pressure. Circ Res. 1990 Jan;66(1):76–83. doi: 10.1161/01.res.66.1.76. [DOI] [PubMed] [Google Scholar]
  19. Nonoguchi H., Knepper M. A., Manganiello V. C. Effects of atrial natriuretic factor on cyclic guanosine monophosphate and cyclic adenosine monophosphate accumulation in microdissected nephron segments from rats. J Clin Invest. 1987 Feb;79(2):500–507. doi: 10.1172/JCI112840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nonoguchi H., Sands J. M., Knepper M. A. Atrial natriuretic factor inhibits vasopressin-stimulated osmotic water permeability in rat inner medullary collecting duct. J Clin Invest. 1988 Oct;82(4):1383–1390. doi: 10.1172/JCI113742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Northridge D. B., Jardine A. G., Alabaster C. T., Barclay P. L., Connell J. M., Dargie H. J., Dilly S. G., Findlay I. N., Lever A. F., Samuels G. M. Effects of UK 69 578: a novel atriopeptidase inhibitor. Lancet. 1989 Sep 9;2(8663):591–593. doi: 10.1016/s0140-6736(89)90714-9. [DOI] [PubMed] [Google Scholar]
  22. Olins G. M., Krieter P. A., Trapani A. J., Spear K. L., Bovy P. R. Specific inhibitors of endopeptidase 24.11 inhibit the metabolism of atrial natriuretic peptides in vitro and in vivo. Mol Cell Endocrinol. 1989 Feb;61(2):201–208. doi: 10.1016/0303-7207(89)90131-7. [DOI] [PubMed] [Google Scholar]
  23. Redfield M. M., Edwards B. S., Heublein D. M., Burnett J. C., Jr Restoration of renal response to atrial natriuretic factor in experimental low-output heart failure. Am J Physiol. 1989 Oct;257(4 Pt 2):R917–R923. doi: 10.1152/ajpregu.1989.257.4.R917. [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. Richards A. M., Cleland J. G., Tonolo G., McIntyre G. D., Leckie B. J., Dargie H. J., Ball S. G., Robertson J. I. Plasma alpha natriuretic peptide in cardiac impairment. Br Med J (Clin Res Ed) 1986 Aug 16;293(6544):409–412. doi: 10.1136/bmj.293.6544.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schütten H. J., Henriksen J. H., Warberg J. Organ extraction of atrial natriuretic peptide (ANP) in man. Significance of sampling site. Clin Physiol. 1987 Apr;7(2):125–132. doi: 10.1111/j.1475-097x.1987.tb00154.x. [DOI] [PubMed] [Google Scholar]
  27. Scriven T. A., Burnett J. C., Jr Effects of synthetic atrial natriuretic peptide on renal function and renin release in acute experimental heart failure. Circulation. 1985 Oct;72(4):892–897. doi: 10.1161/01.cir.72.4.892. [DOI] [PubMed] [Google Scholar]
  28. Seymour A. A., Fennell S. A., Swerdel J. N. Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072. Hypertension. 1989 Jul;14(1):87–97. doi: 10.1161/01.hyp.14.1.87. [DOI] [PubMed] [Google Scholar]
  29. Shimamori Y., Watanabe Y., Fujimoto Y. Specificity of a membrane-bound neutral endopeptidase from rat kidney. Chem Pharm Bull (Tokyo) 1986 Jan;34(1):275–280. doi: 10.1248/cpb.34.275. [DOI] [PubMed] [Google Scholar]
  30. Sonnenberg H., Honrath U., Wilson D. R. In vivo microperfusion of inner medullary collecting duct in rats: effect of amiloride and ANF. Am J Physiol. 1990 Aug;259(2 Pt 2):F222–F226. doi: 10.1152/ajprenal.1990.259.2.F222. [DOI] [PubMed] [Google Scholar]
  31. Sonnenberg J. L., Sakane Y., Jeng A. Y., Koehn J. A., Ansell J. A., Wennogle L. P., Ghai R. D. Identification of protease 3.4.24.11 as the major atrial natriuretic factor degrading enzyme in the rat kidney. Peptides. 1988 Jan-Feb;9(1):173–180. doi: 10.1016/0196-9781(88)90024-1. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Stephenson S. L., Kenny A. J. The hydrolysis of alpha-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11. Biochem J. 1987 Apr 1;243(1):183–187. doi: 10.1042/bj2430183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tonolo G., McMillan M., Polonia J., Pazzola A., Montorsi P., Soro A., Glorioso N., Richards M. A. Plasma clearance and effects of alpha-hANP infused in patients with end-stage renal failure. Am J Physiol. 1988 Jun;254(6 Pt 2):F895–F899. doi: 10.1152/ajprenal.1988.254.6.F895. [DOI] [PubMed] [Google Scholar]
  35. Ura N., Carretero O. A., Erdös E. G. Role of renal endopeptidase 24.11 in kinin metabolism in vitro and in vivo. Kidney Int. 1987 Oct;32(4):507–513. doi: 10.1038/ki.1987.239. [DOI] [PubMed] [Google Scholar]
  36. Weselcouch E. O., Humphrey W. R., Aiken J. W. Effect of pulmonary and renal circulations on activity of atrial natriuretic factor. Am J Physiol. 1985 Nov;249(5 Pt 2):R595–R602. doi: 10.1152/ajpregu.1985.249.5.R595. [DOI] [PubMed] [Google Scholar]
  37. Wilkins M. R., Settle S. L., Stockmann P. T., Needleman P. Maximizing the natriuretic effect of endogenous atriopeptin in a rat model of heart failure. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6465–6469. doi: 10.1073/pnas.87.16.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wong K. R., Xie M. H., Shi L. B., Liu F. Y., Huang C. L., Gardner D. G., Cogan M. G. Urinary cGMP as biological marker of the renal activity of atrial natriuretic factor. Am J Physiol. 1988 Dec;255(6 Pt 2):F1220–F1224. doi: 10.1152/ajprenal.1988.255.6.F1220. [DOI] [PubMed] [Google Scholar]
  39. Woods R. L. Contribution of the kidney to metabolic clearance of atrial natriuretic peptide. Am J Physiol. 1988 Dec;255(6 Pt 1):E934–E941. doi: 10.1152/ajpendo.1988.255.6.E934. [DOI] [PubMed] [Google Scholar]

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

RESOURCES