Cerebral renin-angiotensin mediation of isoproterenol-induced thirst in the dog

Abstract Pretreatment of dogs with s.c. isoproterenol (10 μg/kg) caused a significant increase in drinking when 100 ng renin substrate was administered 3 min later to the lateral cerebral ventricles or subfornical organ. Isoproterenol itself was a potent peripheral (10 μg/kg), but unreliable central (0.01–1 μg) dipsogen. The increased drinking after combined s.c. isoproterenol and intracerebroventricular (i.c.v.) renin substrate injections was significantly attenuated by i.c.v. captopril (20 μg) but was not influenced by s.c. captopril (500 μg/kg). However, combined i.c.v./s.c. pretreatment with captopril nearly abolished drinking to peripheral isoproterenol, or the combination of s.c. isoproterenol and i.c.v. renin substrate. Finally, single intracranial injections of the components of the renin-angiotensin system elicited dose-dependent and site-specific drinking. Renin substrate, angiotensin I and angiotensin III produced greater intakes at forebrain tissue sites than after i.c.v. or subfornical organ injections. Renin, on the other hand, was more potent i.c.v. than at forebrain loci. These results suggest that the cerebral renin-angiotensin system may participate in β-adrenergic thirst mechanisms by increasing local angiotensin II biosynthesis in specific areas of the brain.