Suppression of plasma renin activity by indomethacin in man.
The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PG) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterone relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PG excretion, an indicator of renal PG synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PG synthetase activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000096:biosynthesis; D002986:Clinical Trials as Topic; D003864:Depression, Chemical; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006974:Hypertension, Malignant / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000652:urine; D012083:Renin / Q000097:blood*
D011453:Prostaglandins; D011458:Prostaglandins E; D000804:Angiotensin II; D000450:Aldosterone; D005665:Furosemide; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D007213:Indomethacin