Stroke Related Alterations in the Cerebrovasculature of spSHR Associated with the Loss of Pressure Dependent Constriction
Kyoto Wistar stroke prone spontaneously hypertensive rats (spSHR) fed a Japanese style diet containing 4% NaCl from weaning exhibited a 100% mortality associated with hemorrhagic stroke by 20 weeks of age. The middle cerebral arteries (MCA) from spSHR after stroke and at two ages prior to stroke (before and after 12.5 weeks) were sampled and compared to the MCA of age matched stroke resistant SHR (srSHR). When compared to younger spSHR or srSHR the isolated MCA of prestroke spSHR >12.5 weeks exhibited a decreased ability to constrict to a) elevated pressure b) high levels of [K+]0 (84.6 mM) and c) protein kinase C (PKC) activation (10−6M phorbol dibutyrate), whereas the MCA of poststroke spSHR were unable to constrict to the above vasoactive stimuli. Pressure dependent constriction (PDC) of cerebral arteries is associated with smooth muscle cell depolarization, Ca+2 entery into the muscle through voltage gated Ca+2 channels and the activation of PKC. The decreased ability or inability of MCA from spSHR to constrict to depolarizing stimuli (i.e. elevated [K+]0) and PKC activation prior to and after stroke could account for the attenuation or loss of PDC in these arteries. The loss of PDC prior to stroke may promote the over perfusion of the cerebrovasculature and facilitate the formation of hemorrhagic lesions in spSHR.
KeywordsMiddle Cerebral Artery Hemorrhagic Stroke Lumen Diameter Posterior Cerebral Artery Hemorrhagic Lesion
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