Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure

Patricia G. Cavero, Kenneth B. Margulies, Joseph Winaver, Andrea A. Seymour, Norma G. Delaney, John C Jr. Burnett

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

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<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.

Original languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalCirculation
Volume82
Issue number1
StatePublished - 1990

Fingerprint

Neprilysin
Atrial Natriuretic Factor
Heart Failure
Natriuresis
Sodium
Renal Circulation
Diuresis
Cyclic GMP
Protease Inhibitors
Glomerular Filtration Rate
Lithium
Intravenous Infusions
Arterial Pressure
Hemodynamics
Dogs
Kidney

Keywords

  • Atrial natriuretic factor
  • Kidney
  • Sodium excretion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cavero, P. G., Margulies, K. B., Winaver, J., Seymour, A. A., Delaney, N. G., & Burnett, J. C. J. (1990). Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure. Circulation, 82(1), 196-201.

Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure. / Cavero, Patricia G.; Margulies, Kenneth B.; Winaver, Joseph; Seymour, Andrea A.; Delaney, Norma G.; Burnett, John C Jr.

In: Circulation, Vol. 82, No. 1, 1990, p. 196-201.

Research output: Contribution to journalArticle

Cavero, PG, Margulies, KB, Winaver, J, Seymour, AA, Delaney, NG & Burnett, JCJ 1990, 'Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure', Circulation, vol. 82, no. 1, pp. 196-201.
Cavero PG, Margulies KB, Winaver J, Seymour AA, Delaney NG, Burnett JCJ. Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure. Circulation. 1990;82(1):196-201.
Cavero, Patricia G. ; Margulies, Kenneth B. ; Winaver, Joseph ; Seymour, Andrea A. ; Delaney, Norma G. ; Burnett, John C Jr. / Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure. In: Circulation. 1990 ; Vol. 82, No. 1. pp. 196-201.
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