내피세포를 제거한 흰쥐 대동맥에서 Phenylephrine이 일으킨 수축반응에 대한 alpha-수용체 길항제의 영향

Effects of alpha-Adrenoceptor Antagonists on Phenylephrine-induced Contraction in the Endothelium-denuded Rat Aorta

The effects of an irreversible or a reversible alpha1-adrenoceptor antagonist (dibenamine or prazosin) on alpha1-adrenoceptor-mediated vasoconstrictions were studied in the endothelium-denuded rat aorta. In these experiments, the mobilization of intracelluler calcium and translocation of extracellular calcium were also studied. To exclude the modulation of endothelium releasing EDRF and EDCF, the endothelium was removed in all rat aortas. Contraction induced by phenylephrine (a full alpha1-adrenoceptor agonist) was separated into a fast phasic component of the response due to the release of intracellular calcium and a slow tonic one due to the influx of extracellular calcium. Pretreatments with increasing doses of reversible alpha1-adrenoceptor antagonist prazosin, as well as irreversible alpha1-adrenoceptor antagonist dibenamine, inhibited the phasic component of phenylephrine-induced contraction more effectively than the tonic one. Pretreatment of dibenamine (0.2 mcM) or prazosin (10 nM) to the rat aorta abolished phasic response but remained tonic one about 41% and 51%, respectively. These results suggest that as the efficiency of phenylephrine was progressively reduced by pretreatments with increasing doses of an irreversible or a reversible alpha1-adrenoceptor antagonist (dibenamine or prazosin), the contraction induced by phenylephrine became progressively more dependent on the influx of extracellular calcium.