ENDOTHELINS - A ROLE IN CEREBROVASCULAR-DISEASE

Vasoactive factors produced and released by the endothelium exert a po werful influence on vascular tone in the cerebral circulation. Impaire d endothelium-dependent responses, such as decreased production of end othelium-derived relaxing factors, and/or release of endothelium-deriv ed contractile factors may give rise to different pathophysiological c onditions. Among the endothelium-derived contractile factors the endot helins have recently received particular attention. Endothelin-1 is th e major isoform in the endothelin family, which also includes endothel in-2 and endothelin-3. Endothelin-1 is synthesized within the endothel ium of cerebral vessels, whereas both endothelin-1 and endothelin-3 in addition have been identified in neurons and glia. Recent electrophys iological work has suggested a neuromodulatory role for these peptides ,but at present the general interest is mainly focused on their vasoac tive role. Physiological stimuli such as hypoxia, anoxia, and hemodyna mic shear stress will stimulate the endothelial endothelin production. In the brain, at least two types of specific subreceptors have been c loned; ET(A) receptors, exclusively associated with blood vessels and ET(B) receptors also found on glial, epithelial, and ependymal cells. The endothelins seem so far to be the most potent vasoconstrictors yet identified. The circulating plasma levels of immunoreactive endotheli n are low. Since more than 80% of the total amount released from endot helial cells seems to be secreted towards the underlying smooth muscle , endothelins have been ascribed a local vasoregulatory role. Endothel ins are believed to be involved in several of our most common cerebrov ascular diseases and the present review comments on their possible pat hophysiological role in subarachnoid haemorrhage, cerebral ischemia, a nd migraine.