Single-dose captopril administration in DOCA/salt rats: reduction of hypotensive effect by indomethacin.
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 ng/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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism; D002216:Captopril / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D012083:Renin / Q000097:blood; D012965:Sodium Chloride
D011453:Prostaglandins; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011392:Proline; D002216:Captopril; D012083:Renin; D001920:Bradykinin; D007213:Indomethacin