Analysis of the effects of candesartan on responses to angiotensin II in the hindquarters vascular bed of the cat.

The effects of the nonpeptide angiotensin II (AngII) AT1 receptor blocker candesartan on responses to AngII were investigated in the hindquarters vascular bed of the cat. Under constant-flow conditions, injections of AngII into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Candesartan in a dose of 3 microg/kg intravenously (i.v.) decreased vasoconstrictor responses to AngII in a surmountable manner. At doses of 30 and 300 microg/kg i.v., candesartan shifted the dose-response curve to AngII to the right in an insurmountable manner, indicating an insurmountable blockade of AT1 receptors. The inhibitory effects of the larger doses of candesartan on responses to AngII were long in duration, and the AT1 receptor blocker had little effect on baseline pressures. Candesartan was without effect on vasoconstrictor responses to norepinephrine, U46619, PGF2alpha, vasopressin, BAY K8644; biphasic responses to endothelin-1; or on vasodilator responses to acetylcholine, albuterol, or levcromakalim. These results indicate that candesartan is a potent and selective angiotensin AT1 receptor blocker that can induce both surmountable and insurmountable AT1 receptor blockade and provide support for the hypothesis that there are "spare" AT1 receptors in the hindquarters vascular bed of the cat.