Effects of angiotensin II AT1- or AT2-receptor antagonists on drinking evoked by angiotensin II or water deprivation in rats.
In previous studies, we found that central administration of the AT1-receptor antagonist, EXP 3174, and the AT2-receptor antagonist, PD 123319, blocked the cardiovascular response to centrally-injected angiotensin II (AII), although another AT2-receptor antagonist (PD 123177) was ineffective. In the present study, we examined the effects of these three compounds on the pressor and dipsogenic response to centrally-injected AII in conscious, male Long Evans rats, and the effect of EXP 3174 and PD 123319 on drinking in response to water-deprivation in Brattleboro rats. In Long Evans rats, AII-induced water intake and pressor effects were inhibited by EXP 3174 and PD 123319 (although with different time courses). In contrast, PD 123177 had little effect on the pressor response to i.c.v. AII, but enhanced its dipsogenic action. Following 8 h water deprivation in Brattleboro rats, neither EXP 3174 nor PD 123319 inhibited drinking when water was returned. These data indicate that EXP 3174 and PD 123319 inhibit thirst evoked by centrally injected AII, but not that caused by extracellular dehydration. In addition, since the putative AT2-receptor antagonists PD 123319 and PD 123177 have the opposite effects on i.c.v. AII-induced water intake, these results cannot be easily reconciled with a simple model of thirst in which AT2-receptors are involved in a final common pathway for drinking.
Widdop
R E
RE
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Center, UK.
Gardiner
S M
SM
Bennett
T
T
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004326:Drinking / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011910:Rats, Brattleboro; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology; D014868:Water Deprivation / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; C066026:losartan carboxylic acid; D019808:Losartan