title: Muscle metaboreflex activation during dynamic exercise vasoconstricts ischemic active skeletal muscle.
abstract: Metabolite accumulation due to ischemia of active skeletal muscle stimulates group III/IV chemosensitive afferents eliciting reflex increases in arterial blood pressure and sympathetic activity, termed the muscle metaboreflex. We and others have previously demonstrated sympathetically mediated vasoconstriction of coronary, renal, and forelimb vasculatures with muscle metaboreflex activation (MMA). Whether MMA elicits vasoconstriction of the ischemic muscle from which it originates is unknown. We hypothesized that the vasodilation in active skeletal muscle with imposed ischemia becomes progressively restrained by the increasing sympathetic vasoconstriction during MMA. We activated the metaboreflex during mild dynamic exercise in chronically instrumented canines via graded reductions in hindlimb blood flow (HLBF) before and after α1-adrenergic blockade [prazosin (50 μg/kg)], β-adrenergic blockade [propranolol (2 mg/kg)], and α1 + β-blockade. Hindlimb resistance was calculated as femoral arterial pressure/HLBF. During mild exercise, HLBF must be reduced below a threshold level before the reflex is activated. With initial reductions in HLBF, vasodilation occurred with the imposed ischemia. Once the muscle metaboreflex was elicited, hindlimb resistance increased. This increase in hindlimb resistance was abolished by α1-adrenergic blockade and exacerbated after β-adrenergic blockade. We conclude that metaboreflex activation during submaximal dynamic exercise causes sympathetically mediated α-adrenergic vasoconstriction in ischemic skeletal muscle. This limits the ability of the reflex to improve blood flow to the muscle.
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Jasdeep
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Tiago M
authors.initials: TM
authors.lastname: Machado
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Alberto
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Abhinav C
authors.initials: AC
authors.lastname: Krishnan
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Hanna W
authors.initials: HW
authors.lastname: Hanna
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Yasir H
authors.initials: YH
authors.lastname: Altamimi
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Danielle
authors.initials: D
authors.lastname: Senador
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Marty D
authors.initials: MD
authors.lastname: Spranger
authors.affiliation: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan doleary@med.wayne.edu.
authors.forename: Donal S
authors.initials: DS
authors.lastname: O'Leary
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure; D004285:Dogs; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D005082:Physical Exertion; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012018:Reflex; D012039:Regional Blood Flow; D013564:Sympathetic Nervous System; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D011224:Prazosin
keywords: exercise pressor reflex; ischemic skeletal muscle; metabolic vasodilation; muscle blood flow; sympathetically mediated vasoconstriction; α1- and β-blockade; β2-mediated vasodilation