The cardiovascular effect of intracerebroventricular endothelin in rats

To investigate the cardiovascular action of endothelin within the central nervous system, we studied the effect of intracerebroventricular endothelin in conscious Wistar rats. The endothelin increased blood pressure and the heart rate in a dose-related way. The increase in mean blood pressure produced by 100 ng/kg of endothelin (45 +/- 6 mmHg, mean +/- s.e.m., n = 10) was much greater than that produced by the same amount of intravenous endothelin (4 +/- 1 mmHg, n = 7). Pretreatment with intravenous hexamethonium significantly attenuated the rise in blood pressure elicited by intracerebroventricular endothelin. Combined administration of hexamethonium and a vasopressin antagonist abolished the pressor response. These results indicate that centrally administered endothelin raises blood pressure through activation of the sympathetic nervous system and vasopressin. It is suggested that endothelin may play a role in the central regulation of cardiovascular function.