Novel Endothelial-Mediated Responses Associated with Microcirculation and BBB Function
The importance of endothelial involvement in vascular relaxation induced by acetylcholine drew attention to the role of endothelial mediators in controlling vascular function (Furchgott and Zawadzki, 1980). Since this time, a great number of endothelial factors have been demonstrated to influence not only the vascular tone but also additional parameters including blood flow and blood-brain barrier (BBB) permeability (Rubanyi and Polokoff, 1994; Spatz, et al.,1995a; Gellai, et al.,1997; Thorin, et al.,1998). At the present time, there is substantial agreement that the mechanisms responsible for many of these events involve the interplay among a number of factors in either the circulation or produced locally. Studies in vivo and in vitro have shown that the most potent endothelialderived vasoactive substances, NO and ET-1, are primarily responsible for regulating the vascular reactivity (Gellai, et al.,1997; Bakker, et al.,1997). Our initial studies demonstrated that NO was involved in the postischemic hypoperfusion observed in animal models of cerebral ischemia (Spatz, et al.,1995b). This effect was related to increased levels of ET-1 in the cerebrospinal fluid (CSF). Treatment with ET-1 receptor antagonists abolished the hypoperfusion which resulted in neuronal protection from ischemic damage (Dawson, et al.,1999; Spatz, et al.,1996). These observations highlight the existence of the close relationship between these vasoactive factors and implicate their involvement in maintaining vascular tone and regulating circulation (e.g.,cerebral blood flow and blood pressure) as well as BBB function.
KeywordsAcetylcholine Indomethacin Neuroblastoma Inositol Sorbitol
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