Effect of Losartan,a Nonpeptide Angiotensin II Receptor Antagonist,on Drinking Behavior and Renal Actions of Centrally Administered Renin

Abstract

Losartan, a nonpeptide angiotensin II receptor antagonist, was used to establish the role of brain AT₁ angiotensin II receptor subtype on the natriuretic, antidiuretic, and dipsogenic actions of centrally administered renin. Intracerebroventricular administration of renin reduces urine volume and increases sodium excretion and water intake in conscious, male, hydrated rats. Losartan (3 or 10 mg/kg, sc) reduced the increased sodium excretion and totally inhibited the antidiuretic action induced by intracerebroventricular renin. When both renin and Losartan were given intracerebroventricularly, at the highest dose, there was a potent inhibition of the antidiuretic and natriuretic actions. Peripheral and central administration of the AT₁ receptor blocker significantly lengthened the onset of drinking behavior and reduced the cumulative water intake observed after intracerebroventricular injection of renin.

Our results strongly suggest that the brain AT₁ receptor subtype mediates the physiologic actions of angiotensin II, such as drinking behavior, the increase in sodium excretion, and vasopressin release.