Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension.
To determine whether prostaglandins contribute to the depressor response to the converting enzyme inhibitor, captopril, we measured the plasma prostaglandin levels by radioimmunoassy 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 unmeasurable and that of thromboxane A2 did not change, while the metabolite of PGE2 (PGE-M) increased by 53% (34 +/- 4pg/ml pre-captopril, 52 +/- 5 pg/ml after; p less than 0.001). As expected, blood pressure (BP) and angiotension II (AII levels fell, and kinin levels rose (all changes p less than 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 +/- 3mm Hg pre-synthetase inhibition vs - 13 +/- 2 mm Hg post; p less than 0.05). When these agents did not block the PGE-M response to captopril, the BP response was also unchanged (-15 +/- 4mm Hg pre, -18 +/- 5mm Hg post). Neither indomethacin nor aspirin changed the AII or kinin responses to captopril. We conclude that the prostaglandins may be important mediators of captopril's antihypertensive effect in the sodium-restricted state.
D000328:Adult; D000804:Angiotensin II / Q000097:blood; D001241:Aspirin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D012083:Renin / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011458:Prostaglandins E; D000804:Angiotensin II; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D001241:Aspirin; D007213:Indomethacin