MODULATORY ROLE OF ENDOTHELIAL AND NONENDOTHELIAL NITRIC-OXIDE IN 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION IN CEREBRAL-ARTERIES AFTER SUBARACHNOID HEMORRHAGE

OBJECTIVE: Endothelial dysfunction is claimed to play a role in the pa thogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). We have examined the effect of experimental SAH on the modulat ory action of endothelial and nonendothelial nitric oxide (NO) in the contractile response of goat middle cerebral artery to 5-hydroxytrypta mine (5-HT). METHODS: We compared the Ei-HT-induced contractile respon ses of cerebral arteries from control goats and from goats with SAH th at had been experimentally induced 3 days earlier by delivery of autol ogous arterial blood into the subarachnoid space. Contractile response s were examined by recording the isometric tension in isolated cerebra l arteries. To assess the influence of endothelium, this cell layer wa s mechanically removed in some of the arterial segments (rubbed arteri es) from both control goats and goats with SAH. RESULTS: In arteries f rom control goats, contractile responses to 5-HT were significantly hi gher in rubbed arteries than in arteries with intact endothelium; 5-HT -induced contractions were significantly enhanced by a competitive inh ibitor of NO synthesis, NC-nitro-L-arginine, in arteries both with and without endothelium. In arteries from goats with SAH, 5-HT contracted cerebral arteries without showing significant differences between seg ments with endothelium and those that had been rubbed; in both cases, 5-HT-induced contractions were significantly higher than those obtaine d in arteries from control goats. NG-Nitro-L-arginine significantly en hanced the contractile response to 5-HT of cerebral arteries from goat s with SAH. CONCLUSION: These results suggest that cerebral arteries a fter SAH exhibit hyperreactivity to 5-HT via a mechanism that involves the absence of the modulatory role of endothelial NO, that SAH does n ot modify the modulatory role of nonendothelial NO, and that impairmen t of the modulatory action of endothelial NO on vascular responses to 5-HT could contribute to the pathogenesis of cerebral vasospasm after SAH.