ROLE OF EXTRACELLULAR CA2-INDUCED SPASM OF THE RABBIT BASILAR ARTERY(IN SUBARACHNOID HEMORRHAGE)

Background and Purpose The role of extracellular Ca2+ in the maintenan ce of chronic vasospasm after subarachnoid hemorrhage (SAH) is largely unknown. Indeed, studies thus far have been limited to demonstrations that L-type Ca2+-channel antagonists were unable to reverse the spasm . This study tested whether SAH-induced vasospasm is maintained, at le ast in part, through the influx of extracellular Ca2+ and whether the influx of extracellular Ca2+ occurs through L-type Ca2+ channels and p ossibly, in addition, through store operated channels (SOCs). Furtherm ore, as there is considerable evidence in the literature to suggest th at the spasm is mediated through endothelin-1 (ET-1) release, we teste d whether the Ca2+ dependency of the spasm was consistent with the med iation of the spasm by ET-1. Methods Chronic spasm of the basilar arte ry was induced in a double SAH rabbit model. Relaxation of SAH-, ET-1- , serotonin-, and KCl-constricted basilar artery in response to Ca2+ f ree solution, verapamil, and Ni2+ was measured in situ with the use of a cranial window. Results SAH induced 23% constriction of the basilar artery. Ca2+-free solution and 1 mu mol/L verapamil reversed the cons triction of SAH vessels by 60% and 17%, respectively. In contrast, con trol vessels challenged with 40 to 50 mmol/L KCl, which induced 34% co nstriction, relaxed in response to Ca2+-free solution and verapamil by 98% and 89%, respectively. In SAH vessels, verapamil followed by 0.1 mmol/L Ni2+, which is known to block SOCs, induced a combined relaxati on of 67%. Control vessels challenged with 3 nmol/L ET-1, which induce d a magnitude of constriction similar to that of SAH (29%), relaxed in response to Ca2+-free solution, verapamil, and verapamil plus Ni2+ by 69%, 20%, and 50%, respectively (P>.05 versus respective values in SA H vessels). In contrast, control vessels challenged with 2 to 8 mu mol /L serotonin, which induced a magnitude of constriction similar to tho se of SAH and ET-1 (22%), completely relaxed in response to Ca2+-free solution and verapamil. Conclusions These results demonstrate that the maintenance of chronic spasm in the two-hemorrhage rabbit model after SAH is due to smooth muscle cell contractile mechanisms partly depend ent on the influx of extracellular Ca2+. The influx of extracellular C a2+ results from the opening of L-type Ca2+ channels and an additional channel or channels. We speculate that the L-type Ca2+ channel-indepe ndent influx of extracellular Ca2+ results from the opening of SDCs. T he Ca2+-dependent characteristics of the spasm likely reflect the medi ation of the spasm by ET-1.