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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}}}$</mml:annotation></mml:semantics> </mml:math> ), leg muscle microvascular oxygenation ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>S</mml:mi> <mml:mrow><mml:mi>t</mml:mi> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:mrow> </mml:msub> <mml:annotation>${S_{{\mathrm{t}}{{\mathrm{O}}_2}}}$</mml:annotation></mml:semantics> </mml:math> ; near-infrared spectroscopy) and time to exhaustion. Leg muscle <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>S</mml:mi> <mml:mrow><mml:mi>t</mml:mi> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:mrow> </mml:msub> <mml:annotation>${S_{{\mathrm{t}}{{\mathrm{O}}_2}}}$</mml:annotation></mml:semantics> </mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}}}$</mml:annotation></mml:semantics> </mml:math> or leg muscle <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>S</mml:mi> <mml:mrow><mml:mi>t</mml:mi> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:mrow> </mml:msub> <mml:annotation>${S_{{\mathrm{t}}{{\mathrm{O}}_2}}}$</mml:annotation></mml:semantics> </mml:math> from rest to moderate or severe exercise between conditions (P > 0.05 for all). Moreover, there was no significant difference in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>S</mml:mi> <mml:mrow><mml:mi>t</mml:mi> <mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> </mml:mrow> </mml:msub> <mml:annotation>${S_{{\mathrm{t}}{{\mathrm{O}}_2}}}$</mml:annotation></mml:semantics> </mml:math> 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.