Pharmacological Analysis of Vasodilator Responses to Alpha₂-Adrenoceptor Agonists in Isolated Rat Common Carotid Arteries

Abstract

Using the cannula inserting method, vasodilator responses to alpha₂-adrenoceptor agonists (clonidine, guanabenz, DJ7141 and xylazine) were investigated in isolated and perfused rat common carotid arteries. Alpha₂-adrenoceptor agonists dose-dependently induced a vasodilation in preparations preconstricted by noradrenaline. The potencies were in the order of clonidine>guanabenz>DJ-7141 ≥ xylazine. Removal of the endothelium inhibited ACh-induced vasodilation, but not the alpha₂-agonist-induced dilation. Atropine treatment inhibited AChinduced vasodilation, but not the alpha₂-agonist-induced dilation. Alpha₂-agonist-induced dilations were not modified by beta-blockade, which significantly suppressed isoprenaline-induced vasodilations. The potent alpha₂-adrenoceptor antagonist DG5128 did not influence the alpha₂-agonist-induced vasodilation. In preparations preconstricted by PGF_2α, clonidine and xylazine never induced a vasodilation, and clonidine frequently induced vasoconstrictions that were completely blocked by bunazosin. It is concluded that alpha₂-adrenoceptor agonist-induced vasodilation is independent from the existence of the endothelium, and that it is not related to vascular beta- and alpha₂-adrenoceptors and muscarinic receptors, suggesting that the alpha₂-adrenoceptor agonist-induced vasodilation is due to an antagonistic activity towards the vascular alpha₁ -adrenoceptors.