Abstract

Studies were performed on isolated cerebral and peripheral arterial segments from the rat to define contractile receptors for 5-hydroxytryptamine (5-HT) and to elucidate the responses to calcium channel blockers in relation to their effects on potassium-induced contractions. 5-HT induced strong contraction of the middle cerebral artery, arteries forming the circle of Willis, basilar artery and tail artery in the mentioned order of relative potency and with an intrinsic activity in the brain vessels approximately 70% of that caused by 124 mM potassium in the buffer solution. Ketanserin inhibited the contraction both in the basilar and tail arteries competitively, with pA2 = 9.35 and 9.09, respectively, suggesting mediation by 5-HT2 receptors. The inhibition by cyproheptadine and methysergide (of the response in the basilar artery) was noncompetitive. High potassium in the buffer solution contracted the basilar and tail arteries biphasically, including prazosin-sensitive alpha-adrenoceptor activation in the latter. Cyproheptadine, nimodipine, verapamil and diltiazem inhibited the 5-HT-induced contraction in the mentioned order of potency. Verapamil was more potent than diltiazem, also in the tail artery, but nimodipine inhibited the contraction only by 35%. Also the (tonic) contraction induced by high potassium concentration was attenuated, with the same relative potency as in the presence of 5-HT except for cyproheptadine, which was less efficient than nimodipine. The transient potassium-induced contraction was inhibited less effectively by the calcium antagonists. The IC50 values were characteristically lower in the basilar than in the tail artery, irrespective of whether the contraction had been produced by 5-HT or high potassium.(ABSTRACT TRUNCATED AT 250 WORDS)