Central losartan blocks natriuretic, vasopressin, and pressor responses to central hypertonic NaCl in sheep

Abstract

This study investigated the effect of intracerebroventricular administration of the angiotensin AT1 receptor antagonist losartan on the natriuresis, pressor effect, and arginine vasopressin (AVP) secretion caused by intracerebroventricular infusion of either ANG II, hypertonic saline, or carbachol. Losartan (1 mg/h) or artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle before, during, and after infusions of either ANG II at 10 μg/h for 1 h, 0.75 mol/l NaCl at 50 μl/min for 20 min, or carbachol at 1.66 μg/min for 15 min. Intracerebroventricular infusions of ANG II, 0.75 mol/l NaCl, or carbachol caused increases in renal Na+ and K+ excretion, arterial pressure, and plasma AVP levels. Increases in arterial pressure, Na+ excretion, and plasma AVP concentration ([AVP]) in response to intracerebroventricular ANG II or intracerebroventricular 0.75 mol/l NaCl were either abolished or attenuated by intracerebroventricular infusion of losartan but not by intracerebroventricular infusion of artificial CSF or intravenous losartan. Intracerebroventricular losartan did not reduce the increase in plasma [AVP] or arterial pressure in response to intracerebroventricular carbachol, but it did attenuate the natriuretic response to intracerebroventricular carbachol. We conclude that an intracerebroventricular dose of losartan (1 mg/h) that inhibits responses to intracerebroventricular ANG II also inhibits vasopressin secretion, natriuresis, and the pressor response to intracerebroventricular hypertonic saline. These results suggest that common neural pathways are involved in the responses induced by intracerebroventricular administration of ANG II and intracerebroventricular hypertonic NaCl. We propose that intracerebroventricular infusion of hypertonic saline activates angiotensinergic pathways in the central nervous system subserving the regulation of fluid and electrolyte balance and arterial pressure in sheep.

Early changes of hypothalamic angiotensin II receptors expression in gestational protein-restricted offspring: effect on water intake, blood pressure and renal sodium handling

“…7,15,20,[34][35][36][37][38][39] Our data support recent studies demonstrating that i.c.v. AngII can elicit a significant increase of plasma AVP and c-fos expression without altered plasma osmolality, sodium and hematocrit levels in rats.…”

Brain Angiotensin and Body Fluid Homeostasis.

“…Recent studies in rats and sheep show that central administration of the AT 1 receptor antagonist, losartan, blocks all these responses to ICV hypertonic saline, indicating a central angiotensinergic influence in osmoregulation [52,[56][57][58][59][60]. Moreover, ICV administration of losartan in cattle reduces an osmotically dependent drinking response, specifically, the drinking that follows water deprivation [61].…”

Review: AT1-receptors in the central nervous system

“…113,115 The rapid natriuresis following ICV injection of Ang II may come about because BP increases (causing a pressure natriuresis), renal sympathetic nerve activity is suppressed, 79 plasma levels of renin fall, 116 vasopressin secretion increases, 105,117 or a natriuretic agent is released into the circulation. One of these factors, alone or in combination with one or more of the others, may be the link between brain and kidney mediating this response.…”