The antihypertensive effect of captopril in essential hypertension: relationship to prostaglandins and the kallikrein-kinin system.
Two groups, each with nine essential hypertensive patients, were maintained on 10 mmol sodium daily over 14-17 days and treated in this sequence: placebo; captopril (25 or 50 mg given thrice daily) or indomethacin (50 mg given thrice daily) alone; captopril plus indomethacin, and (4) captopril alone. The initial fall in mean blood pressure induced by captopril (118 +/- 1 to 102 +/- 1 mmHg) was unaffected by the addition of indomethacin. However, if indomethacin treatment preceded captopril, the antihypertensive effect was attenuated (116 +/- 4 to 109 +/- 4), and was associated with significant reductions in urinary prostaglandin and kinin excretion. Addition of captopril to indomethacin returned kinin excretion to placebo levels but did not affect indomethacin-induced reduction in prostaglandin excretion. Captopril alone stimulated plasma renin activity (PRA) fivefold; aldosterone excretion was lowered by 25% and further reduced by indomethacin. Thus, when captopril and indomethacin are administered together, the order of administration is critical to the antihypertensive effect of captopril.
Quilley
J
J
Duchin
K L
KL
Hudes
E M
EM
McGiff
J C
JC
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000652:urine; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use; D007610:Kallikreins / Q000652:urine*; D007705:Kinins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000378:metabolism; D011453:Prostaglandins / Q000652:urine*; D012084:Renin-Angiotensin System; D012964:Sodium / Q000378:metabolism
D007705:Kinins; D011453:Prostaglandins; D002216:Captopril; D012964:Sodium; D003404:Creatinine; D007610:Kallikreins; D011188:Potassium; D007213:Indomethacin