Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans

Evidence in healthy animals and humans is accumulating that the muscle mechanoreceptors play an important role in mediating sympathetic activation during exercise, especially rhythmic exercise. Furthermore, muscle mechanoreceptors appear to be sensitized acutely during exercise by metabolic by-products, although the identity of these by-products remains unknown. The purpose of this study was to determine whether the metabolic by-products 1) prostaglandins and/or 2) adenosine sensitize muscle mechanoreceptor control of muscle sympathetic nerve activity (MSNA) in normal humans during rhythmic exercise. MSNA was recorded using microneurography. Muscle mechanoreceptors were activated by low-level rhythmic forearm exercise for 3 min. In 16 healthy humans, intra-arterial indomethacin was infused into the exercising arm to inhibit synthesis of cyclooxygenase products. In 18 healthy humans, intra-arterial aminophylline was infused into the exercising arm to block adenosine receptors. During saline control, MSNA increased significantly during exercise. Inhibition of cyclooxygenase during exercise dramatically and virtually completely eliminated the reflex sympathetic activation. Inhibition of adenosine receptors with aminophylline had no effect on the sympathetic activation during muscle mechanoreceptor stimulation. In conclusion, muscle mechanoreceptors are sensitized by cyclooxygenase products, but not by adenosine, during 3 min of low-level rhythmic handgrip exercise in healthy humans. Further studies of other metabolic by-products and of patients with enhanced muscle mechanoreceptor sensitivity, such as patients with heart failure, are warranted.