Myogenic Tone as a Therapeutic Target for Ischemic Stroke
Sara M. Palomares and Marilyn J. Cipolla
Affiliation: Department of Neurological Sciences, University of Vermont, 149 Beaumont Ave., HSRF 416A, Burlington, VT 05405.
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 the 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 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 channel (SKCa and IKCa, respectively) inhibition, suggesting basal
endothelium-derived hyperpolarizing factor (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
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