Cyclooxygenase inhibition attenuates muscle sympathetic nerve responses to passive muscle stretch

Abstract

Previous studies suggest the muscle metabolites may sensitize muscle mechanoreceptors. However, the responsible substance(s) has not been studied thoroughly in humans. This study tested the hypothesis that local cyclooxygenase (COX) inhibition in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to passive muscle stretch during post exercise muscle ischemia (PEMI). Responses of blood pressure (BP), heart rate, and MSNA to passive stretch of hand and forearm muscles were assessed in 13 healthy subjects during PEMI before and after COX inhibition by local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block significantly decreased the synthesis of COX products. Before ketorolac Bier block, passive stretch evoked significant increase in MSNA (P<0.005) and mean BP (P<0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P=0.11) or in mean BP (P=0.83). Saline Bier block did not attenuate the MSNA responses. These observations indicate that COX inhibition attenuates MSNA responses to stretch during PEMI, and suggest that COX products sensitize muscle mechanoreceptors in humans. Supported by NIH P01 HL077670, M01 RR010732 and AHA 0635245 N.