Effects of systemic and intracranial inhibition of angiotensin-converting enzyme on isoproterenol-induced drinking in the rat

We have investigated the effects of separate and combined s.c. and intracerebroventricular (i.c.v.) injections of captopril, an inhibitor of angiotensin I-converting enzyme, on isoproterenol-induced thirst. Whereas s.c. injections of captopril (0.5 mg/kg) increased drinking, combined s.c. and i.c.v. (20 μg) injections of captopril nearly abolished drinking to isoproterenol (0.1 mg/kg s.c.). This inhibition was not caused by general debility of the rats since the same treatment did not reduce drinking to 12 h water deprivation. Intracerebroventricular injection of 20 μg captopril alone also greatly reduced isoproterenol-induced drinking, perhaps because it leaked into the circulation; captopril i.c.v. also reduced the pressor response to i.v. injection of hog renin (0.1 Gold blattUnit) by about 65%. These results support the hypothesis that the renin-angiotensin system participates in the stimulation of drinking by isoproterenol and that the enhancement of drinking caused by inhibition of CE only in the circulation is the result of increased synthesis of angiotensin II in the brain.