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 micrograms.kg-1.h-1) to Inactin-anesthetized, sham-operated control rats resulted in dose-dependent increases in urine 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 micrograms.kg-1.h-1, fractional excretion of Na (FENa) 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Abassi
Z
Z
Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion, Haifa, Israel.
Haramati
A
A
Hoffman
A
A
Burnett
J C
JC
Winaver
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D002303:Cardiac Output, Low / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D009320:Atrial Natriuretic Factor