Acute angiotensin II type 1 (AT 1)-receptor blockade exerts differential effects on the vascular and adrenal response to exogenous angiotensin II in man

Abstract

Data from experimental animals suggest that aldosterone stimulation by angiotensin II (AII) may not exclusively be mediated by the AT1-receptor. In the present study, we have therefore investigated the vascular and adrenal response to AII infusion without and with pretreatment with the AT1-receptor antagonist valsartan (160mg) in 9 healthy men. AII was administered intravenously at doses of 1, 3 and 10 ng kg-1min-1, each over 45 min. Arterial blood pressure was measured oscillometrically at 5 minute intervals. Blood for the determination of plasma renin activity (PRA) and plasma aldosterone was taken before the start of the infusion, at the end of each infusion period and one hour after the infusion was stopped. AII induced an increase in systolic/diastolic blood pressure from 121±3/70±2 mmHg to a maximum of 146±2/97±1 mmHg (p<0.001). These changes were paralleled by significant increases in plasma aldosterone from 39.2±9.8 to 290.7±48.3 (p<0.001) and a parallel decrease in PRA. The increase in blood pressure and the decrease in heart rate following exogenous AII were completely abolished in volunteers pretreated with valsartan. Thus, arterial blood pressure averaged 118±3/72±1 mmHg by the end of the maximum AII infusion dose. In contrast, aldosterone stimulation by exogenous AII was only partially blunted by concomitant AT1-receptor blockade (98.9±16.3 pg/ml following the maximal dose of AII). These results suggest that the vascular response to exogenous AII is exclusively mediated by the AT1-receptor. Our data are compatible with the concept that the effects of AII on adrenal aldosterone release may involve other pathways, possibly the AT2-receptor.