DECREASED ENDOTHELIUM-DEPENDENT RELAXATION IN SUBARACHNOID HEMORRHAGE-INDUCED VASOSPASM - ROLE OF ET-1

The purpose of this study was to test whether endothelium-dependent re laxation is decreased during acute vasospasm following subarachnoid he morrhage (SAH) and the mechanism underlying the decrease. Basilar arte ry in situ was 35% constricted 3 days following injection of autologou s arterial blood into the rabbit cisterna magna compared with vessels from control rabbits. In situ suffusion with the endothelium-dependent relaxant, acetylcholine (ACh; 10 mu M), relaxed resting and serotonin (5-HT)-contracted control vessels but not vasospastic and 5-HT-contra cted vasospastic vessels. In contrast, the relaxant potency and effica cy of ACh was similar in control and vasospastic vessels contracted wi th 5-HT in vitro. In situ suffusion with the ET(A)-receptor antagonist , BQ-123 (1 mu M), reversed the vasospasm by 51% and restored the magn itude of ACh relaxation of vasospastic and 5-HT-contracted vasospastic vessels to that of controls. ACh in situ and in vitro relaxed endothe lin-1 (ET-1)-contracted control vessels to a smaller magnitude than 5- HT-contracted control vessels. These results suggest, in contrast to p revious studies, that endothelium-dependent relaxation is decreased du ring acute vasospasm following SAH. The decreased endothelium-dependen t relaxation is secondary to the underlying ET-1-mediated spasm. The i nhibition of endothelium-dependent relaxation observed in situ followi ng SAH cannot be demonstrated in vitro, presumably due to loss of the ET-1-mediated vasospasm.