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(Stroke. 1996;27:1896-1902.)
© 1996 American Heart Association, Inc.

Articles

Role of Extracellular Ca²⁺ in Subarachnoid Hemorrhage-Induced Spasm of the Rabbit Basilar Artery

Mario Zuccarello, MD; Riccardo Boccaletti, MD; Metiner Tosun, BS Robert M. Rapoport, PhD

the Departments of Neurosurgery (M.Z., R.B.) and Pharmacology & Cell Biophysics (R.B., M.T., R.M.R.), University of Cincinnati College of Medicine, and Veterans Affairs Medical Center, Cincinnati, Ohio.

Correspondence and reprint requests to Robert M. Rapoport, PhD, Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Bethesda Ave, Cincinnati, OH 45267-0575.

Background and Purpose The role of extracellular Ca²⁺ in the maintenance 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 least in part, through the influx of extracellular Ca²⁺ and whether the influx of extracellular Ca²⁺ occurs through L-type Ca²⁺ channels and possibly, in addition, through store operated channels (SOCs). Furthermore, as there is considerable evidence in the literature to suggest that the spasm is mediated through endothelin-1 (ET-1) release, we tested whether the Ca²⁺ dependency of the spasm was consistent with the mediation of the spasm by ET-1.

Methods Chronic spasm of the basilar artery was induced in a double SAH rabbit model. Relaxation of SAH-, ET-1-, serotonin-, and KCl-constricted basilar artery in response to Ca²⁺-free 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 µmol/L verapamil reversed the constriction of SAH vessels by 60% and 17%, respectively. In contrast, control vessels challenged with 40 to 50 mmol/L KCl, which induced 34% constriction, 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 relaxation of 67%. Control vessels challenged with 3 nmol/L ET-1, which induced 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 SAH vessels). In contrast, control vessels challenged with 2 to 8 µmol/L serotonin, which induced a magnitude of constriction similar to those 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 dependent on the influx of extracellular Ca²⁺. The influx of extracellular Ca²⁺ results from the opening of L-type Ca²⁺ channels and an additional channel or channels. We speculate that the L-type Ca²⁺ channel-independent influx of extracellular Ca²⁺ results from the opening of SOCs. The Ca²⁺-dependent characteristics of the spasm likely reflect the mediation of the spasm by ET-1.

Editorial Comment

John A. Bevan, MD, Guest Editor

Department of PharmacologyUniversity of VermontBurlington, Vt

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