Contribution of Prostaglandins to the antihypertensive action of captopril in essential hypertension

Abstract

To determine whether prostaglandins contribute to the depressor response to the converting enzyme inhibitor, captopril, we measured the plasma prostaglandln levels by radioimmunoassay before and after captopril administration, and then examined the effect of prostaglandin synthetase inhibition on captopril's antihypertensive effect. When a single oral captopril dose (25-100 mg) was given to 31 sodium-restricted patients with essential hypertension, the levels of the stable transformation product of prostacyclin remained immeasurable and that of thromboxane A, did not change, while the metabolite of PGE, (PGE-M) increased by 53% (34 ± 4 pg/ml pre-captopril, 52 ± 5 pg/ral after; p < 0.001). As expected, blood pressure (BP) and angiotensin II (AH) levels fell, and kinin levels rose (all changesp < 0.001). We then blocked prostaglandin synthesis in 18 of these subjects for 24 hours with either indomethacin (n = 10) or aspirin (n = 8) before repeating the captopril dose, to assess the importance of these PGE-M increments. The PGE-M responses to captopril were effectively blocked in nine of 10 subjects receiving indomethacin and four of eight receiving aspirin. In these 13 patients, the depressor response to captopril was significantly blunted (- 20 ± 3 mm Hg pre-synthetase inhibition vs - 13 ± 2 mm Hg post; p < 0.05). When these agents did not block the PGE-M response to captopril, the BP response was also unchanged (-15 ± 4 mm Hg pre, -18 ± 5 mm Hg post). Neither indomethacin nor aspirin changed the AH or kinin responses to captopril. We conclude that the prostaglandins may be important mediators of captopril's antihypertensive effect in the sodium-restricted state. © 1981 American Heart Association, Inc.