Mechanism of Captopril-Induced Renin Release in Conscious Rats

Abstract

Abstract

The increase in plasma renin activity after angiotensin I-converting enzyme inhibition by Captopril (SQ 14225) is well documented. In a study of the mechanism of Captopril-induced renin release, conscious rats were treated with Captopril (100 mg/kg per day) in their drinking water. Plasma renin activity (PRA) rose sixfold to a plateau after 5 days. At the end of 5 days of treatment with Captopril, rats carrying Alzet osmotic minipumps which infused angiotensin II (ANG II) at 200 ng/kg per min intraperitoneally had a slightly elevated PRA, as opposed to a greatly suppressed one, in ANG II-infused controls (P < 0.05). Urinary prostaglandin ((PG)E₂) daily excretion was unchanged by dietary Captopril. Indomethacin (5 mg/kg) injected subcutaneously significantly reduced plasma PGE₂ after 90 min, whereas PRA in Captopril-treated rats was unchanged after indomethacin injection. Results were similar in ANG II-infused Captopril-treated rats. Propranolol (10 mg/kg) injected intraperitoneally significantly reduced PRA 45 min later, but the PRA of ANG II-infused rats was not lower after propranolol injection under Captopril treatment than in similar rats not infused with ANG II. Indomethacin did not potentiate the effects of propranolol or propranolol plus ANG II on PRA of Captopril-treated rats. In conclusion, Captopril increased renin secretion by β-adrenergically mediated activation of the sympathetic nervous system and by interruption of the short feeback loop of ANG II. PGs did not appear to be involved. Other factors may be operating, since propranolol plus ANG II did not normalize PRA.