Electromechanical Alterations in the Cerebrovasculature of Stroke-Prone Rats

Abstract

Background and Purpose —Cerebrovascular pressure-dependent constriction (PDC) is associated with smooth muscle (SM) depolarization and Ca 2+ influx through voltage-gated channels. We studied the alterations in electromechanical contraction in the middle cerebral arteries (MCAs) of stroke-prone Wistar-Kyoto spontaneously hypertensive rats (SHRsp) in relation to the stroke-related loss of PDC. Methods —Constriction to pressure, elevated [K + ] o and/or [Ca 2+ ] o , and SM membrane potentials (E m ) were measured in isolated pressurized MCAs of SHRsp and stroke-resistant SHR. Results —MCAs of SHRsp exhibited an age-related decrease in PDC before hemorrhagic stroke and a loss of PDC after stroke. At 100 mm Hg, the MCAs of poststroke SHRsp maintained partial constriction that was not altered with pressure but was inhibited by nifedipine (1 μmol/L). The MCAs of poststroke SHRsp constricted to vasopressin (0.17 μmol/L) but not to elevated [K + ] o . When pressure was reduced from 100 to 0 mm Hg, the MCAs from young prestroke SHRsp exhibited SM hyperpolarization (−38 to −46 mV), whereas those of poststroke SHRsp maintained a constant, depolarized E m (−34 mV). Alterations in E m with varying [K + ] o suggested that there was a decrease in SM K + conductance in the MCAs of poststroke SHRsp. Conclusions —The observation that the MCAs of poststroke SHRsp depolarize but do not constrict to elevated [K + ] o suggests the presence of dysfunctional voltage-gated Ca 2+ channels. The inability to alter E m with pressure or to constrict to depolarization could partially contribute to the loss of PDC in the MCAs of poststroke SHRsp.