Low sodium and furosemide-induced stimulation of the renin system in man is mediated by cyclooxygenase 2.
The aim of this study was to examine the effects of highly selective inhibition of cyclooxygenase 2 (COX-2) with rofecoxib on the renin system during long-term stimulation and after short-term stimulation. Six healthy male volunteers received, in a randomized crossover design, a low-sodium diet for days 1 through 9 with or without 25 mg rofecoxib twice daily on days 5 through 9 and, in addition, 20 mg of furosemide intravenously on day 8. Plasma renin activity increased 2 to 3 times over baseline with a low-sodium diet and 5 times over baseline 30 minutes after intravenous furosemide; it was still elevated nearly 5 times on day 9. These effects were completely blocked by rofecoxib. Plasma aldosterone and urinary aldosterone concentrations basically reflected the findings with plasma renin activity. Urinary sodium excretion decreased during a low-sodium diet and increased after intravenous furosemide without being significantly affected by rofecoxib. We have concluded that low-sodium and furosemide-stimulated renin and aldosterone secretion is completely blocked in healthy volunteers during COX-2 inhibition with rofecoxib, suggesting that intact COX-2 is of major importance for stimulation of the renin system under these conditions in man.
Kammerl
M C
MC
Institut für Physiologie, Universität Regensburg, Regensburg, Germany. martin.kammerl@klinik.uni-regensburg.de
Nüsing
R M
RM
Schweda
F
F
Endemann
D
D
Stubanus
M
M
Kees
F
F
Lackner
K J
KJ
Fischereder
M
M
Krämer
B K
BK
D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D015232:Dinoprostone / Q000652:urine; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000652:urine; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004232:Diuretics; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D003404:Creatinine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D015232:Dinoprostone