Effect of selective inhibition of the inducible cyclooxygenase on renin release in healthy volunteers.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) can block renin release via inhibition of cyclooxygenase (COX). The responsible COX-isoenzyme in man is unknown. Therefore, we assessed the effects of meloxicam, a selective inhibitor of COX-2, and indomethacin, an unselective inhibitor of COX-1 and COX-2, on furosemide stimulated plasma renin activity (PRA).


METHODS
In a randomized cross-over design 15 healthy female volunteers received no NSAID or meloxicam 7.5 mg/d for 6 days or indomethacin 25 mg tid for 2 days and 25 mg on the 3rd day. On the control day and on the last day of each treatment the following parameters were evaluated before and after furosemide 20 mg i.v.: PRA measured by RIA, urinary excretion of prostaglandin E2 (PGE2) assessed by gas chromatography-tandem mass spectrometry, urine volume and urinary excretion of sodium, potassium, and creatinine, and serum concentrations of sodium, potassium, and creatinine.


RESULTS
Furosemide led to a more than two-fold rise of PRA. Indomethacin as well as meloxicam had no significant effect on basal PRA but inhibited the furosemide-stimulated PRA increase. PGE2 excretion on the control day rose two-fold after furosemide. Meloxicam had no effect on basal PGE2 excretion, whereas indomethacin reduced this parameter by 30%. Both drugs inhibited the increase of urinary PGE2 after furosemide. No drug effects on urine flow nor on electrolytes and creatinine in serum and urine could be observed.


CONCLUSIONS
Meloxicam inhibited furosemide stimulated renin release, suggesting that in man COX-2 is responsible for prostaglandin synthesis mediating renin release.
Stichtenoth
D O
DO
Institute of Clinical Pharmacology, Hannover Medical School, Germany.
Wagner
B
B
Frölich
J C
JC
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood / Q000652:urine; D005260:Female; D005665:Furosemide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D000077239:Meloxicam; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011863:Radioimmunoassay; D012016:Reference Values; D012083:Renin / Q000097:blood*; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D005665:Furosemide; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D015232:Dinoprostone; D000077239:Meloxicam; D007213:Indomethacin