title: Taming the "sleeping giant": the role of endothelin-1 in the regulation of skeletal muscle blood flow and arterial blood pressure during exercise.
abstract: The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin (ET)-1, the body's most potent vasoconstrictor, participates in this response is unknown. Thus, in eight young (24 ± 2 yr), healthy volunteers, we examined leg blood flow, MAP, tissue oxygenation, heart rate, leg arterial-venous O(2) difference, leg O(2) consumption, pH, and net ET-1 and lactate release at rest and during knee extensor exercise (0, 5, 10, 15, 20, and 30 W) before and after an intra-arterial infusion of BQ-123 [ET subtype A (ET(A)) receptor antagonist]. At rest, BQ-123 did not evoke a change in leg blood flow or MAP. During exercise, net ET-1 release across the exercising leg increased approximately threefold. BQ-123 increased leg blood flow by ~20% across all work rates (changes of 113 ± 76, 176 ± 83, 304 ± 108, 364 ± 130, 502 ± 117, and 570 ± 178 ml/min at 0, 5, 10, 15, 20, and 30 W, respectively) and attenuated the exercise-induced increase in MAP by ~6%. The increase in leg blood flow was accompanied by a ~9% increase in leg O(2) consumption with an unchanged arterial-venous O(2) difference and deoxyhemoglobin, suggesting a decline in intramuscular efficiency after ET(A) receptor blockade. Together, these findings identify a significant role of the ET-1 pathway in the cardiovascular response to exercise, implicating vasoconstriction via the ET(A) receptor as an important mechanism for both the restraint of blood flow in the exercising limb and maintenance of MAP in healthy, young adults.
authors.affiliation: Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84148, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Barrett-O'Keefe
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: Garrett
authors.initials: G
authors.lastname: Morgan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rossman
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Sean
authors.initials: S
authors.lastname: Runnels
authors.forename: David E
authors.initials: DE
authors.lastname: Morgan
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Gmelch
authors.forename: Amber D
authors.initials: AD
authors.lastname: Bledsoe
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
mesh_terms: D000328:Adult; D062186:Arterial Pressure / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D015444:Exercise; D006339:Heart Rate; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007261:Infusions, Intra-Arterial; D019344:Lactic Acid / Q000378:metabolism; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption; D010456:Peptides, Cyclic / Q000008:administration & dosage; D044022:Receptor, Endothelin A / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D055815:Young Adult
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D019344:Lactic Acid; C072247:cyclo(Trp-Asp-Pro-Val-Leu)