Endothelin related pathophysiology in cerebral vasospasm: what happens to the cerebral vessels?
The central role of Endothelin (ET) in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is supported by several investigations. These investigations provided, furthermore, that changes of the ET-receptor expression and function in the wall of the cerebral arteries are a considerable factor for the development of CVS. The biological activity of ET-1 is mediated by two receptor subtypes, named ET(A) and ET(B). Under physiological conditions the dominant vasocontractile effect of ET-1 is mediated by ET(A)-receptors on smooth muscle cells (SMC), which is attenuated by an ET(B)-receptor dependent release of nitric oxide (NO) from endothelial cells (EC). In the physiological cerebrovasculature ECs express exclusively ET(B)- and SMCs only ET(A)-receptors. In case of CVS an increased expression of the ET(B)-receptor could be detected in cerebral vessels. However, the loss of the vasodilative and the missing of a vasocontractile ET(B)-receptor mediated effect was demonstrated. Therefore, any ET(B)-receptor mediated vasoactivity seems to be lost in case of CVS and the biological impact of the increased expression remains unclear so far. The ET(A)-receptor expression seems to be not increased during the development of CVS. Therefore, the proven increase of the ET-dependent vasocontractility seems to be rather by the loss of the ET(B)-receptor mediated effect than by an increased ET(A)-receptor activity. In spite of the more significant changes of the ET(B)-receptor expression the pathophysiological effect of ET, namely the vasoconstriction, seems to be exclusively mediated by the ET(A)-receptor. Therefore, tailored approaches for the treatment of CVS remain to be ET(A)-receptor selective antagonists.
Department of Neurosurgery, Center of Clinical Neurosciences, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. H.Vatter@em.uni-frankfurt.de
Hartmut
H
Vatter
Jürgen
J
Konczalla
Volker
V
Seifert
D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000528:radiation effects*; D016232:Endothelins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D017466:Receptors, Endothelin / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000150:complications; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000473:pathology*
D016232:Endothelins; D017466:Receptors, Endothelin