Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone

Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which pref erentially blocks cyclo-oxygenase-2. activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different f rom those of indomethacin on exercise-induced changes in renal function and the renin-aldosterone system. In a randomized fashion, ten subjects were s tud led after indomethacin (100 mg), nabumetone ( 1 g) or no medication (co ntrol) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% an d 75% of the maximal oxygen uptake rate, and subsequently during two l-h re covery periods. Heart rate, arterial blood pressure, cardiac output and pla sma catecholamines at rest and during exercise were not altered by indometh acin or nabumetone. Indomethacin decreased urinary rates of excretion of 6- oxo-prostaglandin F-1 alpha(6-oxo-PGF(1 alpha)) and thromboxane B-2 in all study periods. Nabumetone decreased 6-oxo-PGF(1 alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomet hacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not n abumetone, decreased sodium excretion, urine flow rate and free water clear ance. The renal response to exercise, however, remained unchanged. In contr ast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF( 1 alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific ex ercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angio tensin II and thromboxane A(2) synthesis may, during exercise, counterbalan ce renal vasoconstriction caused by blockade of vasodilatory prostaglandins .