Chronic angiotensin converting enzyme inhibition enhances renal vascular responsiveness to acetylcholine in anaesthetized rabbits

Objective: To determine whether 6 weeks continuous treatment with an angiotensin converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo, since this treatment results in extensive phenotypic conversion of afferent arteriolar cells from contractile to endocrine-like, renin secretory cells. Methods: Enalapril (10 μg/kg per h s.c.) was delivered continuously for 6 weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and renal blood flow were measured and renal responsiveness tested by constructing dose-response curves to bolus doses of phenylephrine, angiotensin II and acetylcholine delivered directly into the renal artery. Results: ACE inhibition resulted in a significant shift to the left in the renal vascular conductance responses to acetylcholine (P <0.005) and angiotensin II (P <0.05), indicating enhanced, not reduced, responsiveness to these agents. There were no significant effects of chronic ACE inhibition on the conductance responses to phenylephrine. Conclusions: Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce renal vascular responsiveness to three vasoactive agents, suggesting that the phenotypic changes observed in the afferent arterioles and to a lesser extent the interlobular arteries, were either insignificant or compensated for by other changes in renal circulatory control.