TY - JOUR
T1 - Mechanisms of sympathetic restraint in human skeletal muscle during exercise
T2 - Role of α-adrenergic and nonadrenergic mechanisms
AU - Hansen, Alexander B.
AU - Moralez, Gilbert
AU - Romero, Steven A.
AU - Gasho, Christopher
AU - Tymko, Michael M.
AU - Ainslie, Philip N.
AU - Hofstatter, Florian
AU - Rainer, Simon L.
AU - Lawley, Justin S.
AU - Hearon, Christopher M.
N1 - Funding Information:
This work was supported by the Department of Sport Science, University of Innsbruck (to A.B.H., F.H., S.L.R., and J.S.L.), The Wilderness Medical Society research in-training grant (to G.M.), and by National Heart, Lung, and Blood Institute Grant 1F32-HL1-37285-0 (to C.M.H.). Some of the work contained in this study was supported by a Canada Research Chair (P.N.A.) and the Natural Sciences and Engineering Research Council of Canada (to M.M.T. and P.N.A.).
Publisher Copyright:
© 2020 the American Physiological Society.
PY - 2020/7
Y1 - 2020/7
N2 - Mechanisms of sympathetic restraint in human skeletal muscle during exercise: Role of α-adrenergic and nonadrenergic mechanisms. Am J Physiol Heart Circ Physiol 319: H192-H202, 2020. First published June 5, 2020; doi:10.1152/ajpheart.00208.2020.-Sympathetic vasoconstriction is mediated by α-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 α-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 α- A nd β-adrenoreceptors via phentolamine and propranolol, respectively. Cycle exercise caused vasoconstriction in the inactive forearm that was attenuated ~80% with adrenoreceptor blockade (%ΔFVR, +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 ~40% (ΔFVC 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 α-adrenergic signaling. These findings highlight that α-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 α-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 α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction 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 α-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 α-adrenergic receptors.
AB - Mechanisms of sympathetic restraint in human skeletal muscle during exercise: Role of α-adrenergic and nonadrenergic mechanisms. Am J Physiol Heart Circ Physiol 319: H192-H202, 2020. First published June 5, 2020; doi:10.1152/ajpheart.00208.2020.-Sympathetic vasoconstriction is mediated by α-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 α-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 α- A nd β-adrenoreceptors via phentolamine and propranolol, respectively. Cycle exercise caused vasoconstriction in the inactive forearm that was attenuated ~80% with adrenoreceptor blockade (%ΔFVR, +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 ~40% (ΔFVC 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 α-adrenergic signaling. These findings highlight that α-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 α-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 α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction 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 α-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 α-adrenergic receptors.
KW - Cardiovascular reflex
KW - Exercise
KW - Sympathetic nervous system
KW - α-adrenergic receptors
UR - http://www.scopus.com/inward/record.url?scp=85087532391&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00208.2020
DO - 10.1152/ajpheart.00208.2020
M3 - Article
C2 - 32502375
AN - SCOPUS:85087532391
SN - 0363-6135
VL - 319
SP - H192-H202
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1
ER -