Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms

Sympathetic vasoconstriction is mediated by alpha-adrenergic receptors under resting conditions. During exercise, increased sympathetic nerve activity (SNA) is directed to inactive and active skeletal muscle; however, it is unclear what mechanism(s) are responsible for vasoconstriction during large muscle mass exercise in humans. The aim of this study was to determine the contribution of alpha-adrenergic receptors to sympathetic restraint of inactive skeletal muscle and active skeletal muscle during cycle exercise in healthy humans. In ten male participants (18-35 yr). mean arterial pressure (intra-arterial catheter) and forearm vascular resistance (FVR) and conductance (FVC) were assessed during cycle exercise (60% total peak workload) alone and during combined cycle exercise + handgrip exercise (HGE) before and after intra-arterial blockade of alpha-and beta-adrenoreceptors via phentolamine and propranolol, respectively. Cycle exercise caused vasoconstriction in the inactive forearm that was attenuated similar to 80% with adrenoreceptor blockade (%Delta FVR, +81.7 +/- 84.6 vs. +9.7 +/- 30.7%; P = 0.05). When HGE was performed during cycle exercise, the vasodilatory response to HGE was restrained by similar to 40% (Delta FVC HGE, +139.3 +/- 67.0 vs. cycle exercise: +81.9 +/- 66.3 ml.min(-1) .100 mmHg(-1); P = 0.03); however, the restraint of active skeletal muscle blood flow was not due to a-adrenergic signaling. These findings highlight that alpha-adrenergic receptors are the primary, but not the exclusive mechanism by which sympathetic vasoconstriction occurs in inactive and active skeletal muscle during exercise. Metabolic activity or higher sympathetic firing frequencies may alter the contribution of alpha-adrenergic receptors to sympathetic vasoconstriction. Finally, nonadrenergic vasoconstrictor mechanisms may be important for understanding the regulation of blood flow during exercise. NEW & NOTEWORTHY Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of alpha-adrenergic receptors. Furthermore, exercise-induced vaso-constriction restrains the subsequent vasodilatory response to handgrip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that alpha-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of alpha-adrenergic receptors.