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.
Chiba
S
S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Tsukada
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*; D014991:Xylazine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D014991:Xylazine; C032368:midaglizole; D001285:Atropine; D011433:Propranolol; D015237:Dinoprost; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine