Pharmacological analysis of vasodilator responses to alpha 2-adrenoceptor agonists in isolated rat common carotid arteries.

Using the cannula inserting method, vasodilator responses to alpha 2-adrenoceptor agonists (clonidine, guanabenz, DJ7141 and xylazine) were investigated in isolated and perfused rat common carotid arteries. Alpha 2-adrenoceptor agonists dose-dependently induced a vasodilation in preparations preconstricted by noradrenaline. The potencies were in the order of clonidine greater than guanabenz greater than DJ-7141 greater than or equal to xylazine. Removal of the endothelium inhibited ACh-induced vasodilation, but not the alpha 2-agonist-induced dilation. Atropine treatment inhibited ACh-induced vasodilation, but not the alpha 2-agonist-induced dilation. Alpha 2-agonist-induced dilations were not modified by beta-blockade, which significantly suppressed isoprenaline-induced vasodilations. The potent alpha 2-adrenoceptor antagonist DG5128 did not influence the alpha 2-agonist-induced vasodilation. In preparations preconstricted by PGF2 alpha, clonidine and xylazine never induced a vasodilation, and clonidine frequently induced vasoconstrictions that were completely blocked by bunazosin. It is concluded that alpha 2-adrenoceptor agonist-induced vasodilation is independent from the existence of the endothelium, and that it is not related to vascular beta- and alpha 2-adrenoceptors and muscarinic receptors, suggesting that the alpha 2-adrenoceptor agonist-induced vasodilation is due to an antagonistic activity towards the vascular alpha 1-adrenoceptors.