Interaction of calmodulin antagonists with α-adrenergic responses in pithed rats and in the perfused hindquarters of the rat

Abstract The effect of calmodulin antagonists was studied on the α 1 - and α 2 -adrenoceptor-mediated increase in diastolic blood pressure in pithed rats and on the α 1 -adrenoceptor-mediated reduction of flow in the perfused hindquarters of the rat. B-HT 920 was used as a selective α 2 -adrenoceptor agonist in the pithed rat experiments, whereas cirazoline was used as a selective agonist for α 1 -adrenoceptors. The latter was used after pretreatment with nifedipine (1 mg/kg) or phenoxybenzamine (30 μg/kg), revealing calcium influx-insensitive and -sensitive mechanisms of vasoconstriction, respectively. Papaverine, calmidazolium and W-7 did not influence the dose-response curves for the agonists in the pithed rat experiments. The modest effects of high doses of flunarizine and bepridil on the dose-response curve for B-HT 920 and of trifluoperazine on the dose-response curve for cirazoline can be explained by the well-known calcium entry (flunarizine) and α 1 -adrenoceptor-blocking (bepridil) effects of these drugs. Bepridil and calmidazolium caused an elevation of the cirazoline dose-response curves in the perfused rat hindquarters; flunarizine and trifluoperazine showed a parallel and dose-dependent displacement of the cirazoline dose-response curve to the right, whereas W-7 was inactive. Our results do not implicate calmodulin-associated effects in the α-adrenoceptor-mediated vasoconstriction in pithed rats and in the perfused rat hindquarters.