Centrally administered losartan inhibits the reduction in plasma renin concentration caused by intracerebroventricular hypertonic saline in Na-depleted sheep.
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.
McKinley
M J
MJ
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Mathai
M L
ML
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004234:Diuretics, Osmotic / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D019808:Losartan; D010052:Ovariectomy; D012083:Renin / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D012964:Sodium / Q000172:deficiency*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013012:Sorbitol / Q000008:administration & dosage / Q000494:pharmacology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014667:Vasopressins / Q000097:blood
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004234:Diuretics, Osmotic; D007093:Imidazoles; D012462:Saline Solution, Hypertonic; D013777:Tetrazoles; D014667:Vasopressins; D012965:Sodium Chloride; D013012:Sorbitol; D012964:Sodium; D012083:Renin; D019808:Losartan