Chronic Losartan treatment blocks isoproterenol-induced dipsogenesis.
Previous studies suggest that beta-adrenergic receptor agonists and other hypotensive agents stimulate water intake via the renin-angiotensin system (RAS). However, a recent study reported that acute peripheral administration of Losartan, an angiotensin II (AII) type I receptor antagonist, failed to inhibit isoproterenol-induced water intake. In the current study we assessed the role of chronic Losartan treatment on isoproterenol-induced water intake. Male Sprague-Dawley rats were divided into two groups (n = 10/group). The experimental group was chronically treated with Losartan in the drinking water (120 mg/kg/day). Rats in the control group were maintained on normal tap water. At the end of each week, water intake in response to isoproterenol was determined. On the days of the dipsogenic study, water intake was determined 1 h prior to and 2 h following SC injection of isoproterenol (25 micrograms/kg). Isoproterenol-induced water intake in the experimental group was significantly lower than the control rats by 71% and 88% at the end of weeks one and two respectively (p < 0.01). Following ten days of Losartan treatment, dipsogenic response to AII likewise demonstrated a complete blockage of AII receptors (75% decrease compared to the controls). These data strongly suggest that water intake in response to isoproterenol is mediated in part by the RAS.
Iyer
S N
SN
Department of Pharmacodynamics, College of Pharmacy, JHMHC, University of Florida, Gainesville 32610, USA.
Wright
B E
BE
Strubbe
G
G
Hanley
K
K
Katovich
M J
MJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019808:Losartan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan; D007545:Isoproterenol