Effects of endothelin on blood vessels of the brain and choroid plexus

Endothelin is a recently described vasoactive peptide produced by endothelial cells. Receptors for endothelin are found throughout the brain, and are particularly dense in the choroid plexus. Effects of endothelin on cerebral blood flow and blood flow to the choroid plexus are not known. In this study, we examined effects of endothelin (100 and 1000 ng/kg i.v.) on regional blood flow (microspheres) and cerebral microvascular pressure in anesthetized rabbits. Endothelin (1000 ng/kg) produced only a 4 +/- 2 mm Hg (mean +/- S.E.M.) increase in systemic blood pressure, and had no effect on cerebral blood flow or cerebral microvascular pressure. In contrast, endothelin produced a marked decrease in blood flow to the choroid plexus and dura mater. Blood flow to choroid and dura remained significantly decreased 1 h after administration of the peptide. Endothelin also reduced blood flow to the kidney and small intestine, but the decreases tended to be less than in choroid plexus or dura mater. Thus, circulating endothelin, at doses that have no effect on cerebral blood vessels, has marked effects on blood flow to the choroid plexus. These findings suggest that circulating or locally produced endothelin may contribute to regulation of brain fluid balance through effects on choroid plexus and production of cerebrospinal fluid.