Low sodium and furosemide-induced stimulation of the renin system in man is mediated by cyclooxygenase 2.

Author(s): Kammerl MC, Nusing RM, Schweda F, Endemann D, Stubanus M, Kees F, Lackner KJ, Fischereder M, Kramer BK

Affiliation(s): Institut fur Physiologie, Universitat Regensburg, Regensburg, Germany. martin.kammerl@klinik.uni-regensburg.de

Publication date & source: 2001-11, Clin Pharmacol Ther., 70(5):468-74.

Publication type: Clinical Trial; Randomized Controlled Trial

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.