Central effects of endothelin-1 on vasopressin release, blood pressure, and renal solute excretion.

Abstract

To assess central effects of endothelin-1 (ET-1) on plasma arginine vasopressin (AVP), plasma atrial natriuretic peptide (ANP), blood pressure, heart rate, and renal solute excretion, ET-1 dissolved in the artificial cerebrospinal fluid was infused intracerebroventricularly (icv) at a dose of either 0.35 ng.kg-1.min-1 (0.14 pmol; LET) or 3.5 ng.kg-1.min-1 (1.4 pmol; HET) for 45 min in conscious rats. In the control study, ET-1 was omitted from the vehicle. Moreover, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-O-methyl-tyrosine]AVP (TMeAVP), a V1-blocker, and prazosin, an alpha 1-blocker, were peripherally administered. In the LET group, mean arterial blood pressure (MABP) increased without any changes in heart rate, plasma AVP and ANP, and renal solute excretion. In the HET group, MABP markedly increased with rises in plasma AVP and ANP, but urine flow, urinary osmolality, and urinary Na and K excretion decreased. TMeAVP attenuated the pressor response to ET-1, abolished rises in plasma ANP, and partially restored falls in urine flow. Prazosin after TMeAVP obviated the pressor response to ET-1. In the control, these parameters did not change, except for an increase in urinary solute excretion. These results showed that icv ET-1 stimulates the sympathetic nervous activity and plasma AVP, leading to increased blood pressure and renal vasoconstriction, with a reduction in renal water and electrolyte excretion.