The renin-angiotensin system in drinking and cardiovascular responses to isoprenaline in the rat.

1. We investigated the role of the renin-angiotensin system in isoprenaline-induced drinking in the rat. Captopril, an inhibitor of angiotensin-converting enzyme, was used to block the synthesis of angiotensin II either in the circulation alone or in the brain as well.2. Subcutaneous injections of isoprenaline (0.1 mg/kg) alone caused nine rats to drink 8.4 +/- 0.9 ml water in 3 h.3. Pre-treatment with doses of captopril (0.1-1.0 mg/kg, s.c.), which inhibit conversion of angiotensin I to II in the circulation but not in the brain, dose-dependently enhanced the drinking response to isoprenaline. Captopril alone did not cause drinking.4. Higher doses of captopril (5.0-100 mg/kg, s.c.), which inhibit conversion of angiotensin I to II in the brain as well as in the blood, caused dose-dependent inhibition of drinking elicited by isoprenaline.5. The highest dose of captopril tested (100 mg/kg, s.c.) completely blocked the drinking response to isoprenaline (0.1 or 0.33 mg/kg, s.c.) for at least 45 min. This inhibition was not caused by general debility of the rats; animals deprived of water (12 h) and treated with both captopril and isoprenaline drank as much as water-deprived controls.6. We found no evidence that blocking the renin-angiotensin system inhibits drinking because it exacerbates isoprenaline-induced hypotension. After injection of isoprenaline the mean arterial pressure of nephrectomized rats or rats pre-treated with the high dose (100 mg/kg, s.c.) of captopril (which blocked drinking) was only slightly lower (5-10 mmHg) than that of rats pre-treated with the low dose (0.5 mg/kg, s.c.) of captopril (which enhanced drinking).7. Water deprivation, which caused rats treated with isoprenaline and captopril to drink, did not increase arterial pressure. Pitressin increased the arterial pressure of rats treated with isoprenaline and captopril but did not cause drinking. We conclude that the renin-angiotensin system has a direct and essential role in the drinking response to isoprenaline.