Single-Dose Captopril Administration in DOCA/Salt Rats: Reduction of Hypotensive Effect by Indomethacin

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Abstract
The effect of an oral angiotensin I converting enzyme inhibitor, SQ 14225 (Captopril) on blood pressure and plasma renin activity (PRA) was studied in deoxycorticosterone-salt (DOCA/salt) hypertensive rats. Intraperitoneal (ip) injection of captopril (1 mg/kg) produced a significant fall in systolic blood pressure (23.4 ± 5.0 mm Hg, p < 0.001) whereas no significant change in blood pressure occurred in control rats. Indomethacin (IDM) (2.5 mg/kg ip) pretreatment significantly (p < 0.01) attenuated the hypotensive action of captopril in DOCA/salt rats. PRA was markedly suppressed in DOCA/salt rats (0.3 ± 0.1 mg/ml/hr) when compared with the normotensive controls (4.4 ± 2.2 ng/ml/hr, p < 0.001) at baseline. Captopril induced a significant rise in PRA in both groups of rats. These responses were not significantly altered by IDM pretreatment. The hypotensive effect of captopril in the DOCA/salt model may be mediated by prostaglandins since their synthesis is inhibited by indomethacin.