RELAXATION OF SUBARACHNOID HEMORRHAGE-INDUCED SPASM OF RABBIT BASILARARTERY BY THE K+ CHANNEL ACTIVATOR CROMAKALIM

Background and Purpose Cerebral vasospasm resulting from subarachnoid hemorrhage (SAH) is refractory to most vasodilators. However, despite evidence that a mechanism underlying the vasospasm may be smooth muscl e cell membrane depolarization resulting from decreased K+ conductance , the ability of K+ channel activators to relax the spasm has not been thoroughly investigated. The purpose of this study, therefore, was to investigate whether K+ channel activation selectively relaxes SAH-ind uced vasospasm. Methods Three days after SAH in the rabbit, relaxation of the basilar artery in response to the KC channel activator cromaka lim as well as to staurosporine (protein kinase C antagonist), forskol in (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase activator) was measured in situ with the use of a cranial wind ow. Relaxation in response to these agents was also investigated in co ntrol vessels contracted with serotonin. Membrane potential of the smo oth muscle cells of the basilar artery from SAH and control rabbit was measured in vitro with the use of intracellular microelectrodes. Resu lts Cromakalim completely relaxed the SAH-induced spastic basilar arte ry, while staurosporine, forskolin, and sodium nitroprusside were sign ificantly less efficacious. In contrast, sodium nitroprusside and fors kolin were more efficacious relaxants in serotonin-contracted control vessels than in SAH vessels. The K+ channel blocker glyburide and high [K-L] prevented cromakalim-induced relaxation. Glyburide did not inhi bit forskolin-induced relaxation of serotonin-contracted control vesse ls. Cromakalim concentration-dependently repolarized spastic basilar a rtery smooth muscle cells, and the repolarization was prevented by gly buride. Conclusions These results suggest that K+ channel activation s electively relaxes SAH-induced vasospasm. We speculate that the abilit y of K+ channel activators to selectively relax the spasm may be due, at least in part, to the underlying inhibition of K+ channels after SA H.