MECHANISMS OF CENTRALLY ADMINISTERED ET-1-INDUCED INCREASES IN SYSTEMIC ARTERIAL-PRESSURE AND AVP SECRETION

Endothelins (ET) within the central nervous system (CNS) alter systemi c cardiovascular responses and arginine vasopressin (AVP) secretion. T hese experiments were designed to ascertain whether the rise in system ic arterial pressure after central administration of ET-1 is mediated by enhancing sympathetic outflow and/or circulating AVP. In Long-Evans (LE/LE) rats, intracerebroventricular injection of 1-10 pmol ET-1 dos e dependently increased mean arterial pressure (MAP). Peak response oc curred 7-12 min after ET-1 and was inhibited by ET(A) receptor antagon ism. Systemic vasopressin (V-1) receptor blockade did not inhibit the presser response, and rats with central diabetes insipidus (DI/DI) dis played an identical rise in MAP. Ganglionic blockade prevented ET-1-in duced hemodynamic effects. Peak plasma AVP levels occurred 60 min afte r ET-1, as the presser response began to wane. In sinoaortic-denervate d LE/LE rats, ET-1 elicited a 10-fold increase in AVP secretion that c oincided with the hemodynamic changes and was blocked by BQ-123. Thus ET-1 via ET(A) receptors within the CNS induced a concentration-depend ent increase in systemic arterial pressure mediated by enhanced sympat hetic outflow but not by circulating AVP. Reflex baroreceptor activati on attenuated AVP release.