Mechanisms of rat basilar artery relaxation in health and in a model of subarachnoid hemorrhage
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AbstractCerebral vasospasm is a primary complication after aneurysmal subarachnoid hemorrhage. Despite a great deal of research regarding the pathogenesis of arterial vasospasm, the mechanisms involved still remain poorly understood and, as a result, the treatment strategies employed today have controversial results in the prevention and treatment of this disease. Within the cerebral circulation, the rate of total cerebral blood flow is held within a relatively narrow range, in spite of wide variations of systemic blood pressure. Among the local regulatory mechanisms, a great deal of interest has been focused on the vascular endothelium and potassium channels, with both believed to play a major role in the regulation of vascular tone. Evidence indicates that the abnormalities in cerebrovascular function after subarachnoid hemorrhage, in vivo, may involve alterations m endothelial and/or potassium channel function. The present study was undertaken to examine endothelium-dependent and potassium-induced relaxation of rat basilar artery, as well as the involvement of potassium channels in the relaxation mechanisms, under control conditions and in a single injection rat model of subarachnoid hemorrhage. Effects of vasoactive agonists and potassium channel modulators on basilar artery tone were examined using a wire myograph. This study provides evidence for a decrease in endothelial-dependent relaxation in spite of an apparent increase in eNOS protein expression after subarachnoid hemorrhage in the rat single injection model. We found that nitric oxide synthesis/release in the endothelium is dependent on endothelial membrane potential and this mechanism appears to be altered after subarachnoid hemorrhage. We also demonstrated for the first time that the ability of extracellular potassium to induce relaxation of basilar artery is partly dependent on nitric oxide release from the endothelium. In addition, this study demonstrates an increase in ouabain sensitivity of the tissue as well as a possible decrease in inward rectifier potassium channel expression/function after subarachnoid hemorrhage. Pretreatment with cerebro-spinal fluid from subarachnoid hemorrhage, but not control rats depressed acetylcholine- and authentic nitric oxide-induced relaxation of basilar arteries. Treatment with cerebro-spinal fluid obtained from control rats and rats with subarachnoid hemorrhage induced rapid changes in ouabain sensitivity of the tissue.
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