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) AT(1) receptor blocker candesartan on responses to AngII were investigated in the hindquarters va scular bed of the cat. Under constant-flow conditions, injections of AngII into the hindquarters perfusion circuit elicited dose-dependent increases i n perfusion pressure. Candesartan in a dose of 3 mu g/kg intravenously (iv) decreased vasoconstrictor responses to AngII in a surmountable manner. At doses of 30 and 300 mu g/kg iv, candesartan shifted the dose-response curve to AngII to the right in an insurmountable manner, indicating an insurmoun table blockade of AT(1) receptors, The inhibitory effects of the larger dos es of candesartan on responses to AngII were long in duration, and the AT(1 ) receptor blocker had little effect on baseline pressures. Candesartan was without effect on vasoconstrictor responses to norepinephrine, U46619, PGF (2 alpha), vasopressin, BAY K8644; biphasic responses to endothelin-1; or o n vasodilator responses to acetylcholine, albuterol, or levcromakalim. Thes e results indicate that candesartan is a potent and selective angiotensin A T(1) receptor blocker that can induce both surmountable and insurmountable AT(1) receptor blockade and provide support for the hypothesis that there a re "spare" AT(1) receptors in the hindquarters vascular bed of the cat.