Stroke Development in Stroke-Prone Spontaneously Hypertensive Rats Alters the Ability of Cerebrovascular Muscle to Utilize Internal Ca 2+ to Elicit Constriction

Abstract

Background and Purpose— The ability of middle cerebral arteries (MCAs) to utilize intracellular smooth muscle (SM) Ca 2+ to produce constriction in response to pressure and agonists was assessed in relation to hemorrhagic stroke development in Wistar-Kyoto stroke-prone (SHRSP) and stroke-resistant (srSHR) spontaneously hypertensive rats. Methods— MCAs were studied with the use of a pressure myograph at 100 mm Hg. Results— MCAs from srSHR and prestroke SHRSP exhibited pressure-dependent constriction and constricted in response to vasopressin or serotonin in the presence of nifedipine or the absence of [Ca 2+ ] o . MCAs from poststroke SHRSP lost the latter functions and could only constrict in response to vasopressin/serotonin in Krebs’ solution containing Ca 2+ in the absence of nifedipine. This indicated that the SM could not utilize internal Ca 2+ for constriction and maintained constriction by Ca 2+ entry through L-type channels. The MCAs of poststroke SHRSP could not constrict to [K + ] o -induced depolarization, suggesting that the agonist-induced opening of the L-type channels occurred by mechanisms other than SM depolarization. Depletion of the sarcoplasmic SM Ca 2+ stores of MCAs from srSHR with cyclopiazonic acid did not prevent pressure-dependent constriction. Conclusions— Stroke in SHRSP produced a defect in the ability of MCAs to constrict in response to vasopressin or serotonin via the use of an intracellular source of Ca 2+ . This could be promoted by an inability of the SM to release intracellular Ca 2+ , by the depletion of internal Ca 2+ stores, or by a decrease in the contractile sensitivity to Ca 2+ released from the internal stores.