Inhibitory effects of candesartan on responses to angiotensin peptides in the hindquarters vascular bed of the cat

The effects of the nonpeptide angiotensin II AT(1) receptor antagonist candesartan on responses to angiotensin II were investigated in the hindquarters vascular bed of the cat. Under constant-flow conditions, injections of angiotensin II into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Candesartan in a dose of 3 mu g/kg iv decreased vasoconstrictor responses to angiotensin II in a competitive manner. However, at doses of 10-1000 mu g/kg iv, candesartan shifted the dose-response curve to angiotensin II to the right in a nonparallel manner, suggesting a noncompetitive blockade. The inhibitory effects of candesartan on responses to angiotensin II were long in duration, and the AT(1) receptor antagonist had little effect on baseline pressures. Candesartan was without effect on vasoconstrictor responses to norepinephrine, U46619, PGF(2 alpha), and BAY K8644; on biphasic responses to endothelin-1; and on vasodilator responses to acetylcholine. Candesartan significantly attenuated hindquarters vasoconstrictor responses to angiotensin III and IV with a parallel shift at the 3 mu g/kg iv dose and a nonparallel shift to the right at the high dose of the AT(1) receptor antagonist. The results of the present study indicate that candesartan is a potent angiotensin AT(1) receptor antagonist that can induce both competitive and noncompetitive blockade of responses to angiotensin II, III, and IV in the hindquarters vascular bed of the cat.