Intracerebroventricular losartan inhibits postprandial drinking in sheep.
We investigated the contribution of brain angiotensinergic mechanisms to postprandial drinking in sheep. Sheep in fluid balance were given 0.8 kg chaff for 30 min, and water intake was measured for the next hour. Intracerebroventricular infusion of the AT1 type angiotensin II (ANG II) receptor blocker losartan (1 mg/h) reduced postprandial drinking by approximately 70% (n = 7, P < 0.01) but did not affect food intake. The same losartan dose given intravenously had little or no effect on prandial drinking. Feeding increased Na+ concentrations in plasma and cerebrospinal fluid (CSF; n = 5, P < 0.05). Intracerebroventricular losartan (1 mg/h) inhibited the drinking responses to intracarotid infusion of ANG II (0.8 microg/min for 30 min, n = 4, P < 0.01) and to intracerebroventricular infusion of 0.5 M NaCl (1 ml/h for 1 h, n = 5, P < 0.05) but had no effect on drinking responses to intravenous infusion of 4 M NaCl (1.3 ml/min for 30 min). These findings indicate that a brain ANG II-dependent mechanism is involved in postprandial drinking in sheep. They suggest also that the mechanism by which increasing CSF Na+ causes thirst involves brain ANG II and is different from the mechanism subserving the drinking response to changes in blood Na+.
Mathai
M
M
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Evered
M D
MD
McKinley
M J
MJ
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002339:Carotid Arteries; D002552:Cerebral Ventricles / Q000502:physiology*; D004327:Drinking Behavior / Q000187:drug effects*; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D019808:Losartan; D019518:Postprandial Period; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014882:Water-Electrolyte Balance
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan