Central Effects of Endothelin-1 on Vasopressin and Atrial Natriuretic Peptide Release and Cardiovascular and Renal Function in Conscious Rats

In order to investigate the central effect of endothelin-1 (ET-1) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular and renal function, either a high dose of ET-1 (3.5 ng/kg/min, HET-1) or a low dose (0.35 ng/kg/min, LET-1) was administered into the cerebral third ventricle in conscious rats. ET-1 increased the mean arterial blood pressure, but not heart rate, in a dose-related manner. LET-1 slightly stimulated AVP release, but not ANP release. HET-1 increased plasma AVP and ANP. Pretreatment with a V1-antagonist (TMeAVP) attenuated the blood pressure response to ET-1 and completely abolished increases in plasma ANP. Moreover, prazosin given i.v. completely prevented the residual pressure response. ET-1 did not significantly affect renal electrolytes and water handling. These results suggest that centrally administered ET-1 may increase the activity of the sympathetic nervous system and vasopressinergic neurons, resulting in an increase in blood pressure.