A NONCOMPETITIVE TYPE OF ANGIOTENSIN-RECEPTOR ANTAGONISM BY LOSARTAN IN RENAL-ARTERY PREPARATIONS

In rabbit isolated renal artery preparations angiotensin II (1-100 nM) induced concentration-dependent vasoconstriction. Losartan at lower c oncentrations (3-100 nM) concentration dependently depressed the maxim al responses to angiotensin II. At higher concentrations (0.3 and 1 mu M) losartan only shifted the concentration-response curves for angiot ensin II to the right without further reducing the maximal responses. PD123177 (1 mu M) did not influence angiotensin II-induced contraction s. In rabbit renal artery, AT(1) but not AT(2) receptors appear to med iate the responses to angiotensin II. However, losartan antagonized th e AT(1) receptors in both an insurmountable and a surmountable manner, possibly involving two subpopulations of AT(1) receptors.