Effect of Perindopril on Renal Medullary Hemodynamics in Genetically Hypertensive Rats

Abstract

Early and chronic angiotensin converting enzyme (ACE) inhibition prevents hypertension and improves the pressure natriuresis in Lyon hypertensive (LH) rats. The effect of this treatment on the responses of renal medullary blood flow (MBF) to angiotensin II (Ang II) was studied. In chronic experiments, Ang II (7.5 to 480 ng/kg, intravenous) was injected in 15-week-old anesthetized LH and normotensive (LL) control rats treated orally since weaning with perindopril (0.4 or 1.5 mg/kg/day) with or without pretreatment with indomethacin (5 mg/kg intravenous). In acute experiment, Ang II (30 to 480 ng/kg intravenous) was given in LH rats treated acutely with perindopril (1.5 mg/kg, intravenous bolus). Administration of Ang II induced dose-dependent decreases in MBF, which were greater in LH than in LL rats. In LL rats, the initial and short-lasting (<1 min) medullary vasoconstriction evoked by Ang II was followed by a long-lasting (>2 min) and dose-dependent medullary vasodilation, which was blunted in LH rats. Chronic perindopril treatment normalized the blood pressure level in LH rats and corrected their blunted medullary vasodilation, whereas the same treatment had no significant effect in LL rats. In chronically perindopril-treated LH rats, indomethacin decreased by 90% the medullary vasodilation induced by Ang II. Acute perindopril treatment did not modify the medullary responses to Ang II in LH rats. Chronic ACE inhibition restores the vasodilator response of MBF to Ang II in LH rats. This effect, which is not observed after acute inhibition, is mainly mediated through the release of prostaglandins.