Angiotensin inhibition and atrial natriuretic peptide release after acute volume expansion in rats with aortocaval shunt

Objective: In heart failure atrial natriuretic peptide (ANP) release in res ponse to volume expansion is impaired while the renin-angiotensin system is activated. This study was designed to test the hypothesis that ANP release in heart failure is dependent on an activated angiotensin system. Methods: We studied the ANP and renin-angiotensin systems in a rat model of shunt-i nduced high-output heart failure, in which we rapidly increased circulating fluid volume with a 5 mi, hyperoncotic infusion, and evaluated the effects of acute inhibition of the angiotensin converting enzyme as well as of the blockade of the angiotensin II type 1 receptors on the ANP release and on renal excretory function. Results: ANP and angiotensin II plasma concentrat ions prior to volume expansion were elevated (p<0.05) in rats with aortocav al shunt compared to controls. The diuretic response to acute volume expans ion (18.5+/-1.5 vs. 48.2+/-2.4 mu l/min, p<0.001) was markedly blunted. ANP release was attenuated in rats with aortocaval shunt, as was the increase of its second messenger cGMP in plasma and urine. The blunted increase in A NP plasma levels was not due to depleted cardiac stores as cardiac ANP cont ent, as well as ANP synthesis, were increased (p<0.05). Acute inhibition of the angiotensin converting enzyme as well as blockade of the angiotensin I I type 1 receptors restored ANP release in response to volume expansion (p< 0.02). Moreover, acute inhibition of the renin-angiotensin system completel y normalized the diuretic response. Conclusions: Our data suggest that the ANP system is impaired in rats with aortocaval shunt. The activation of the angiotensin system contributes to the impairment of the ANP system. Acute inhibition of the angiotensin II system significantly improved the ability of the ANP system to respond to acute volume expansion. Our findings indica te a hitherto fore unappreciated interaction between both systems and sugge st additional mechanisms for the beneficial effects of angiotensin converti ng enzyme inhibition or angiotensin II type 1 receptor antagonists in heart failure. (C) 1999 Published by Elsevier Science B.V. All rights reserved.