PREVENTION BY THE NEW CA2-3941, OF LOSS OF ENDOTHELIUM-DEPENDENT RELAXATION AFTER SUBARACHNOID HEMORRHAGE IN RATS( CHANNEL ANTAGONIST, AJ)

AJ-3941 -oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate; CAS No. 143110-70-7), a cerebrovascular-selective Ca2+ channel antagon ist having anti-lipid peroxidative action, was reported to prevent cer ebral vasospasm following subarachnoid hemorrhage in rats. The present study was undertaken to determine whether AJ-3941 protects the impair ment of cerebroarterial endothelium-dependent relaxation which is conc omitantly induced with cerebral vasospasm. Subarachnoid hemorrhage bip hasically suppressed the response to acetylcholine in rat basilar arte ry, at 0.5 h (n = 4; P < 0.06) and 1 day (n = 5; P < 0.05)after subara chnoid hemorrhage. The reduction of the responses was correlated signi ficantly to the degree of vasospasm determined angiographically. This reduction was accompanied by a 49% increase of arterial lipid peroxide contents. Endothelium-independent relaxation in subarachnoid hemorrha ge rats was preserved in response to 3-morpholinosydnonimine, sodium n itroprusside and papaverine. AJ-3941 prevented (n = 6-8, P < 0.05) the suppression of the acetylcholine-induced response and the increase in lipid peroxide content in subarachnoid hemorrhage rats. These results suggest that AJ-3941 could exert its vasospasmolytic effect by preser ving endothelial function through its anti-lipid peroxidative action, in addition to its inhibition of vasospasmogen-induced vasoconstrictio n related to intracellular Ca2+ mobilization.