Effects of acute selective cyclooxygenase-2 inhibition on skeletal muscle microvascular oxygenation and exercise tolerance.

The cyclooxygenase (COX) pathway regulates vascular tone and, therefore, local O₂ delivery-utilization matching. The two main isoforms, COX-1 and COX-2, may promote opposing effects on contracting muscle O₂ transport in health by inducing vasoconstriction and vasodilatation, respectively. Whether COX-2 and its main vasodilatory product (prostacyclin, PGI₂) modulate microvascular O₂ transport to skeletal muscle and thus exercise tolerance is unknown. We tested the hypothesis that acute selective COX-2 inhibition (SC2I) would impair cardiorespiratory and skeletal muscle microvascular responses from rest to exercise, thereby reducing exercise tolerance in healthy adults. Twelve individuals participated in a randomized, double-blind, crossover study to receive SC2I (200 mg celecoxib) or placebo (control, CON). Moderate and severe intensity cycling were performed with measurements of heart rate, arterial blood pressure, pulmonary oxygen uptake ( ${\dot{V}}_{O_2}$ ), leg muscle microvascular oxygenation ( $S_{t{O}_2}$ ; near-infrared spectroscopy) and time to exhaustion. Leg muscle $S_{t{O}_2}$ was also assessed during cuff occlusion protocols. SC2I decreased the plasma concentration of the stable PGI₂ metabolite 6-keto prostaglandin F_1α (CON: 203 (54) pg/mL; SC2I: 108 (54) pg/mL; P = 0.002). There was no difference in exercise tolerance (CON: 278 (55) s; SC2I: 298 (75) s), arterial blood pressure, heart rate, pulmonary ${\dot{V}}_{O_2}$ or leg muscle $S_{t{O}_2}$ from rest to moderate or severe exercise between conditions (P > 0.05 for all). Moreover, there was no significant difference in $S_{t{O}_2}$ during cuff occlusion protocols between conditions. Contrary to our hypothesis, these data indicate that COX-2 is not obligatory for the regulation of skeletal muscle microvascular oxygenation at rest or during moderate or severe intensity exercise, and therefore does not modulate exercise tolerance in healthy adults.