This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cavero, P. G. Articles by Burnett, J. C. Search for Related Content PubMed PubMed Citation Articles by Cavero, P. G. Articles by Burnett, J. C., Jr Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Failure

Circulation, Vol 82, 196-201, Copyright © 1990 by American Heart Association

ARTICLES

Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure

PG Cavero, KB Margulies, J Winaver, AA Seymour, NG Delaney and JC Burnett Jr
Mayo Clinic and Foundation, Rochester, MN 55905.

The present studies were designed to determine the action of neutral endopeptidase inhibition (NEP-I), an inhibitor of the degradation of atrial natriuretic factor (ANF), in congestive heart failure (CHF). Studies were conducted in two groups of anesthetized dogs with CHF induced by 8 days of rapid right ventricular pacing. Group 1 (n = 5) received a specific NEP-I (SQ 28,603) at two doses administered sequentially -30 mg/kg followed by a 60 mg/kg i.v. bolus. Group 2 (n = 5) received intravenous infusion of exogenous ANF (100 ng/kg/min) to achieve increases in plasma ANF concentration as observed in group 1. NEP-I resulted in a diuresis and natriuresis (p less than 0.05) with increases in the fractional excretion of sodium and fractional excretion of lithium, the latter a marker for proximal tubule sodium delivery. Such tubular actions occurred in the absence of increases in glomerular filtration rate or renal blood flow but were associated with significant increases in urinary ANF and urinary cyclic GMP. Plasma ANF increased after the 30 mg/kg NEP-I dose. In contrast, in group 2 with exogenous ANF and despite a marked increase in plasma ANF, no natriuresis was observed. Arterial pressure did not change in either group. These studies demonstrate for the first time in CHF that NEP-I may potentiate the natriuretic action of endogenous ANF by a mechanism that is independent of systemic or renal hemodynamics and does not parallel increases in plasma ANF. These studies support an important therapeutic role for NEP-I in CHF.

This article has been cited by other articles:

				G. Sansoe, M. Aragno, R. Mastrocola, J. C. Cutrin, S. Silvano, G. Mengozzi, A. Smedile, F. Rosina, O. Danni, and M. Rizzetto Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1337 - F1343. [Abstract] [Full Text] [PDF]

				R Ferrara, F Mastrorilli, G Pasanisi, S Censi, N D'aiello, A Fucili, M Valgimigli, and R Ferrari Neurohormonal modulation in chronic heart failure Eur. Heart J. Suppl., April 1, 2002; 4(suppl_D): D3 - D11. [Abstract] [PDF]

				T. Maki, Y. Nasa, F. Yamaguchi, H. Yoshida, M. Mori, T. Takada, E. Horikawa, K. Okano, and S. Takeo Long-term treatment with neutral endopeptidase inhibitor improves cardiac function and reduces natriuretic peptides in rats with chronic heart failure Cardiovasc Res, August 15, 2001; 51(3): 608 - 617. [Abstract] [Full Text] [PDF]

				O. Lisy, J. G. Lainchbury, H. Leskinen, and J. C. Burnett Jr Therapeutic Actions of a New Synthetic Vasoactive and Natriuretic Peptide, Dendroaspis Natriuretic Peptide, in Experimental Severe Congestive Heart Failure Hypertension, April 1, 2001; 37(4): 1089 - 1094. [Abstract] [Full Text] [PDF]

				H. H. Chen, J. A. Grantham, J. A. Schirger, M. Jougasaki, M. M. Redfield, and J. C. Burnett Jr. Subcutaneous administration of brain natriuretic peptide in experimental heart failure J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1706 - 1712. [Abstract] [Full Text] [PDF]

				P. Solter, D. Sisson, W. Thomas, and L. Goetze Intrarenal Effects of Ecadotril during Acute Volume Expansion in Dogs with Congestive Heart Failure J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 989 - 995. [Abstract] [Full Text]

				H. H. Chen, J. A. Schirger, W. L. Chau, M. Jougasaki, O. Lisy, M. M. Redfield, P. T. Barclay, and J. C. Burnett Jr Renal Response to Acute Neutral Endopeptidase Inhibition in Mild and Severe Experimental Heart Failure Circulation, December 14, 1999; 100(24): 2443 - 2448. [Abstract] [Full Text] [PDF]

				B. Geny, H. Hardy, J. Lonsdorfer, B. Eisenmann, P. Haberey, and F. Piquard Enhanced Natriuretic Response to Neutral Endopeptidase Inhibition in Heart-Transplant Recipients Hypertension, April 1, 1999; 33(4): 969 - 974. [Abstract] [Full Text] [PDF]

				M. T. Rademaker, C. J. Charles, T. Kosoglou, A. A. Protter, E. A. Espiner, M. G. Nicholls, and A. M. Richards Clearance receptors and endopeptidase: equal role in natriuretic peptide metabolism in heart failure Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2372 - H2379. [Abstract] [Full Text] [PDF]

				M. Volpe, P. Magri, M. A. E. Rao, S. Cangianiello, L. DeNicola, A. F. Mele, B. Memoli, I. Enea, S. Rubattu, B. Gigante, et al. Intrarenal Determinants of Sodium Retention in Mild Heart Failure : Effects of Angiotensin-Converting Enzyme Inhibition Hypertension, August 1, 1997; 30(2): 168 - 176. [Abstract] [Full Text]

				R. Willenbrock, M. Scheuermann, K. Hohnel, F. C. Luft, and R. Dietz Acute and Chronic Neutral Endopeptidase Inhibition in Rats With Aortocaval Shunt Hypertension, June 1, 1996; 27(6): 1259 - 1266. [Abstract] [Full Text]

				Z. A. Abassi, S. Kotob, E. Golomb, F. Pieruzzi, and H. R. Keiser Pulmonary and Renal Neutral Endopeptidase EC 3.4.24.11 in Rats With Experimental Heart Failure Hypertension, June 1, 1995; 25(6): 1178 - 1184. [Abstract] [Full Text]

				K. B. Margulies, P. L. Barclay, and J. C. Burnett Jr The Role of Neutral Endopeptidase in Dogs With Evolving Congestive Heart Failure Circulation, April 1, 1995; 91(7): 2036 - 2042. [Abstract] [Full Text]

				J. G. Motwani, C. C. Lang, G. Cramb, and A. D. Struthers Natriuretic Response to Neutral Endopeptidase Inhibition Is Blunted by Enalapril in Healthy Men Hypertension, April 1, 1995; 25(4): 637 - 642. [Abstract] [Full Text]