Relaxation of Subarachnoid HemorrhageInduced Spasm of Rabbit Basilar Artery by the K + Channel Activator Cromakalim

Abstract

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 muscle 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-induced vasospasm. Methods Three days after SAH in the rabbit, relaxation of the basilar artery in response to the K + channel activator cromakalim as well as to staurosporine (protein kinase C antagonist), forskolin (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase activator) was measured in situ with the use of a cranial window. Relaxation in response to these agents was also investigated in control vessels contracted with serotonin. Membrane potential of the smooth muscle cells of the basilar artery from SAH and control rabbit was measured in vitro with the use of intracellular microelectrodes. Results Cromakalim completely relaxed the SAH-induced spastic basilar artery, while staurosporine, forskolin, and sodium nitroprusside were significantly less efficacious. In contrast, sodium nitroprusside and forskolin were more efficacious relaxants in serotonin-contracted control vessels than in SAH vessels. The K + channel blocker glyburide and high [K + ] prevented cromakalim-induced relaxation. Glyburide did not inhibit forskolin-induced relaxation of serotonin-contracted control vessels. Cromakalim concentration-dependently repolarized spastic basilar artery smooth muscle cells, and the repolarization was prevented by glyburide. Conclusions These results suggest that K + channel activation selectively relaxes SAH-induced vasospasm. We speculate that the ability of K + channel activators to selectively relax the spasm may be due, at least in part, to the underlying inhibition of K + channels after SAH.