Interaction of calmodulin antagonists with alpha-adrenergic responses in pithed rats and in the perfused hindquarters of the rat.
The effect of calmodulin antagonists was studied on the alpha 1- and alpha 2-adrenoceptor-mediated increase in diastolic blood pressure in pithed rats and on the alpha 1-adrenoceptor-mediated reduction of flow in the perfused hindquarters of the rat. B-HT 920 was used as a selective alpha 2-adrenoceptor agonist in the pithed rat experiments, whereas cirazoline was used as a selective agonist for alpha 1-adrenoceptors. The latter was used after pretreatment with nifedipine (1 mg/kg) or phenoxybenzamine (30 micrograms/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 alpha 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 alpha-adrenoceptor-mediated vasoconstriction in pithed rats and in the perfused rat hindquarters.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D002147:Calmodulin; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C014282:cirazoline