Effects of Flunarizine on Contractile Responses of Porcine Brain Arteries to Various Peripheral Vasoactive Agents

Shin, Se Pyoung; Kim, Jong Moon

Abstract

Effects of various peripheral vasoconstrictors on isolated porcine basilar and posterior communicating arteries(BA and PCA) were investingated and effected of flunarizine on the contractile responses were compared with those of a vasodilator, nitroglycerin. KCl elicited dose-dependent contractions in BA and PCA. 50mM KCl-induced contraction was not affected by nitroglycerin but dose-dependently inhibited by nimodipin and flunarizine in both rings. Epinephrine produced contractile response of BA and PCA in a dose-dependent fashion, but norepinephrine or phenylephrine did not cause obvious contraction by itself. Norepinephrine and phenylephrine elicited dose-dependent contractions in both rings treated with 10 -6M propranolol and the epinephrine-induced contractions were potentiated by pretreatment with propranolol, 5-hydroxytryptamine and histamine contracted BA and PCA in a dose-dependent manner and the contraction of PCA was more prominent than that of BA. In PCA rings, 10(-6)M 5-hydroxytryptamine and 10 -6M orepinephrine-induced contractions were not changed by nitroglycerin but inhibited by flunarizine in a dose-dependent manner. Small doses of flunarizine inhibited gradually both drug-induced contractions and large doses(3.5 x 10(-6) and 10(-6)M) steeply inhibit ed the contractions. Then the slopes of inhibitory curves in both cases were biphasic. Above results suggest that responsibility of catecholamine in porcine brain artery is more prominent in alpha-adrenoceptors than in beta-adrenoceptors, and inhibitory effect of flunarizine on brain artery results from inhibition of calcium influx through stimulated receptor-operated calcium channel(ROC) and potential-operated calcium channel(POC) .