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

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.