Invited Symposium: Stroke/Cerebral Vasospasm
Robert M. Rapoport, PhD (Department of Pharmacology and Cell Biophysics, University of Cincinnati School of Medicine, USA)
Marlo Zuccarello, MD (Department of Neurosurgery, University of Cincinnati School of Medicine, USA)
Endothelins role in a wide variety of vascular diseases and phenomena are widely documented. Endothelin-1 (ET) role in subarachnoid hemorrhage (SAH) induced vasospasm is integral, and is reviewed in this abstract. Clinical investigations revealed increased ET concentrations in the CSF of patients who had suffered SAH. Experimental research revealed administration of ET intracisternally reproduced vasospasm in dogs. A variety of factors cause secretion of ET by endothelial cells in SAH, thus stimulating various ET receptors which influence vasospasm. Blockade of ET-A and ET-B2 receptors leads to prevention and reversal of SAH induced vasospasm, indicating stimulation of these receptors on the vasculature smooth muscle leads to vasoconstriction and thus vasospasm. The ET-B1 receptor also plays an important role in vasospasm. Stimulation of this receptor causes vasodilation. This vasodilation appears to be mediated, at least in part, via nitric oxide. More importantly, ET-B1 receptor stimulation has been shown to induce further ET release by the endothelium. This positive feedback is an important mechanism for the production and maintenance of vasospasm and appears to be the major influence of ET-B receptors role in the production of vasospasm. In summary, a variety of factors stimulate the endothelium to release ET in SAH. ET stimulates both the ET-A receptor, which causes a potent vasoconstriction, and the ET-B1 receptor. ET-B1 receptor stimulation by ET leads to further ET release, and also has the added, less potent effect of nitric oxide release and a vasodilation. ET-B2 receptor is also stimulated, which leads to a further vasoconstriction.
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|Jonathan D. Sherman, MD; Robert M. Rapoport, PhD; Marlo Zuccarello, MD; (1998). The Role of Endothelin-1 in Subarachnoid Hemorrhage-Induced Vasospasm. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/zhang/sherman0594/index.html|
|© 1998 Author(s) Hold Copyright|