Effect of converting-enzyme inhibition on renal response to ANF in rats with experimental heart failure

Z. Abassi, A. Haramati, A. Hoffman, J. C. Burnett, J. Winaver

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Increased activity of the renin-angiotensin system is thought to play a major role in the pathogenesis of salt retention and edema formation in congestive heart failure. The present study evaluates the effects of chronic inhibition of angiotensin-converting enzyme on the response to infusion of exogenous atrial natriuretic factor (ANF) in salt-retaining rats with chronic arteriovenous (a-v) fistula, an experimental model of high-output congestive heart failure. Administration of ANF in incremental doses (5-50 μg·kg-1·h-1) to Inactin-anesthetized, sham-operated control rats resulted in dose-dependent increases in flow, sodium excretion, and glomerular filtration rate, and significant decreases in mean arterial blood pressure. These effects of atrial peptide were markedly attenuated in salt-retaining rats with a-v fistula. However, chronic oral treatment with the angiotensin-converting-enzyme inhibitor enalapril restored the natriuretic response of sodium-retaining rats with a-v fistula to high doses of ANF. At a dose of 50 μg·kg-1·h-1, fractional excretion of Na (FE(Na) in a-v fistula rats given enalapril was 4.0 ± 0.5%, which was significantly greater than that in a-v fistula rats without enalapril (0.5 ± 0.4%, P < 0.05) and not different from the response in sham-control rats (4.9 ± 0.7%). The improvement in the natriuretic response after enalapril was not associated with a significant increase in GFR and occurred despite a decrease in mean arterial pressure. Moreover, chronic enalapril treatment did not significantly alter the plasma levels of immunoreactive ANF in either the sham controls or in the rats with a-v fistula. These data demonstrate that chronic converting-enzyme inhibition restores the natriuretic action of synthetic ANF in anesthetized rats with experimental heart failure. The data further suggest that increased activity of the renin-angiotensin system plays an important role in mediating the blunted natriuretic response to ANF in this experimental model of heart failure.

Original languageEnglish (US)
Pages (from-to)R84-R89
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume259
Issue number1 28-1
StatePublished - Jan 1 1990

Keywords

  • Arteriovenous fistula
  • Atrial natriuretic factor
  • Converting-enzyme inhibitor
  • Kidney function
  • Renin-angiotensin system
  • Sodium reabsorption

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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