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

Abstract

Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin-aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) 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% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF(1alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A(2) synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of vasodilatory prostaglandins.

BOLD-MRI for the assessment of renal oxygenation in humans: Acute effect of nephrotoxic xenobiotics

“…This observation is in line with other studies in humans. Sturrock et al 23 and Olsen et al 24 found neither a change in renal sodium and water handling nor in glomerular filtration rate, effective renal plasma flow, and renal vascular resistance after 2 Â 100 mg indomethacin administration in healthy male subjects.…”

Endothelin A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Are Synergistic via an Endothelin B Receptor–Mediated and Nitric Oxide–Dependent Mechanism

“…The dose is known to inhibit prostaglandin production over the time course of the study, as evidenced by decreased urinary excretion rates of prostaglandins (30). N G -monomethyl-L-arginine (L-NMMA; Clinalfa AG, Laufelfingen, Switzerland) was administered at a dose of 3 mg/kg over 5 min as an NO synthase inhibitor, with each dose of BQ-123, during the relevant study day.…”

Effect of Non-Steroidal Anti-Inflammatory Drugs on Sport Performance Indices in Healthy People: a Meta-Analysis of Randomized Controlled Trials

“…Fortynine articles were fully reviewed; from the bibliography of these six, additional articles were selected and reviewed. Twenty articles were excluded because they did not assess the outcomes of interest, and data could not be extracted from the reported graphs, inadequate intervention; a total of 23 studies were included [17,18,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] (Fig. 1).…”