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Current Vascular Pharmacology
ISSN (Print): 1570-1611
ISSN (Online): 1875-6212
Epub Full Text Article
DOI: 10.2174/15701611113116660155      Price:  $95









Myogenic Tone as a Therapeutic Target for Ischemic Stroke

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Author(s): Sara Morales Palomares and Marilyn J Cipolla
Abstract:
Ischemic stroke causes vascular paralysis and impaired autoregulation in the brain, the degree of which is dependent on the depth and duration of ischemia and reperfusion (I/R). Ischemic stroke also impairs myogenic response of middle cerebral arteries (MCA) that may be an underlying mechanism by which autoregulation is impaired. Myogenic responses are affected by I/R through several mechanisms, including production of peroxynitrite, depolymerization of F-actin in vascular smooth muscle, and circulating vasoactive factors. The vascular endothelium is also significantly affected during focal ischemia that has a particularly large influence on vascular tone in the cerebral circulation. Endothelial nitric oxide (NO) and endothelin-1 (ET-1) are important endothelium-dependent of vasoactive substances that can influence the level of myogenic tone in cerebral arteries and arterioles that are significantly affected during ischemic stroke. Unlike MCA, brain penetrating arterioles have considerable myogenic tone that appears less affected by focal ischemia. The persistent tone of brain parenchymal arterioles during focal ischemia could contribute to perfusion deficit and infarct expansion. These arterioles within the cerebral cortex are also unique from MCA in that they constrict to small– and intermediate-conductance calcium-activated potassium channels (SKCa and IKCa, respectively) inhibition, suggesting basal endothelium-derived hyperpolarizing factors (EDHF) is preserved during focal ischemia. This review will highlight our current understanding of the effects of I/R on myogenic response in both MCA and parenchymal arterioles and discuss underlying mechanisms by which focal ischemia affects myogenic tone in these different vascular segments
Keywords:
Cerebral blow flow, circulating factors, ischemic stroke, middle cerebral arteries, myogenic response, parenchymal arterioles
Affiliation:
Department of Neurology, University of Vermont, 89 Beaumont Ave. Given C454, Burlington, VT 05405