Mechanisms of Skeletal Muscle Contraction‐Induced Rapid Vasodilation in Humans: Role of Vascular Hyperpolarization

Abstract

A monophasic increase in skeletal muscle blood flow is observed following a brief single forearm contraction in humans. Evidence in dogs indicates an obligatory role of vasodilation via smooth muscle hyperpolarization, and recent in situ data suggest that activation of Na+/K+ATPase and KIR channels during muscle contraction contributes to this vasodilation. We tested the hypothesis that inhibition of Na+/K+ATPase and KIR channels via intra‐arterial infusion of ouabain and barium chloride (BaCl2), respectively, and thus vascular hyperpolarization decreases contraction‐induced rapid vasodilation in the human forearm. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10s prior to, and for 30s after a single 1‐s dynamic forearm contraction at 10, 20, and 40% maximum voluntary contraction (MVC) in 12 young adults. Inhibition of hyperpolarization reduced total forearm vasodilation by ~74, 62, and 55% (10, 20, and 40% MVC, respectively). Additional blockade of nitric oxide synthase and cyclooxygenase further attenuated the response to a total reduction of ~80% for all intensities. The present study demonstrates a significant contribution of vascular hyperpolarization to contraction‐induced rapid vasodilation, and that collective blockade of nitric oxide, prostaglandins, and vascular hyperpolarization nearly abolishes this phenomenon in humans.HL102720