The Role of Cerebral Microvessel Endothelium in Regulation of Cerebral Blood Flow Through Production of Endothelin-1

Abstract

We have previously reported the production of endothelin-1 (ET-1) by the cerebral microvessel endothelia and suggested an important role of ET-1 and microvessel endothelia in the regulation of local blood flow within the brain. In the present study, radioimmunoassay of ET-1 revealed that ET-1, produced by cultured cerebral microvessel endothelia grown on a filter, is released mainly to the basal side (corresponding to the basement membrane side), not to the apical side (corresponding to the vascular lumen side). This might indicate that ET-1 constricts arterioles locally at the same place where it is produced by endothelia. The present results also show that cultured cerebral microvessel endothelia produce less ET-1 under low oxygen pressure and that they produce more ET-1 under low carbon dioxide pressure. Taken together, our results may suggest that the negative feedback regulation of cerebral blood flow through oxygen and carbon dioxide pressure is mediated by ET-1 produced locally by cerebral microvessel endothelia.