Centrally administered losartan inhibits the reduction in plasma renin concentration caused by intracerebroventricular hypertonic saline in Na-depleted sheep

Abstract

Infusions (at 1 ml/h) of two different hypertonic solutions were made into the lateral cerebral ventricle of Na-depleted sheep and the effect on plasma renin concentration (PRC) was investigated. Intracerebroventricular (i.c.v.) infusion of 0.75 mol/l NaCl caused a large reduction in plasma renin concentration whereas i.c.v. infusions of hypertonic 1.2 mol/l sorbitol in 0.15 mol/l NaCl or isotonic artificial cerebrospinal fluid did not. An i.c.v. infusion of the angiotensin AT1 receptor antagonist losartan (1 mg/ml per h for 2.5 h) commencing 1 h prior to i.c.v. 0.75 mol/l NaCl prevented the reduction in PRC induced by i.c.v. hypertonic NaCl. No change in arterial pressure occurred with any of these i.c.v. infusions in Na-depleted sheep. The results suggest that a central angiotensinergic mechanism may be involved in central pathways inhibiting renin secretion by the kidney.