title: Exercise-induced inhibition of angiotensin II vasoconstriction in human thigh muscle.
abstract: It is well established that metabolic inhibition of adrenergic vasoconstriction contributes to the maintenance of adequate perfusion to exercising skeletal muscle. However, little is known regarding nonadrenergic vasoconstriction during exercise. We tested the hypothesis that a non-adrenergic vasoconstrictor, angiotensin II (AngII), would be less sensitive to metabolic inhibition than an alpha1-agonist, phenylephrine (PE), in the exercising human thigh. In 11 healthy men, femoral blood flow (FBF, ultrasound Doppler and thermodilution) and blood pressure were evaluated during wide-ranging doses of intra-arterial (femoral) infusions of PE and AngII at rest and during two workloads of steady-state knee-extensor exercise (7 W and 27 W). At rest, the maximal decrease in femoral artery diameter (FAD) during AngII (9.0+/-0.2 to 8.4+/-0.4 mm) was markedly less than during PE (9.0+/-0.3 to 5.7+/-0.5 mm), whereas maximal reductions in FBF and femoral vascular conductance (FVC) were similar during AngII (FBF: -65+/-6 and FVC: -66+/-6%) and PE (-57+/-5 and -59+/-4%). During exercise, FAD was not changed by AngII, but moderately decreased by PE. The maximal reductions in FBF and FVC were blunted during exercise compared to rest for both AngII (7 W: -28+/-5 and -40+/-5%; 27 W: -15+/-4% and -29+/-5%) and PE (7 W: -30+/-4 and -37+/-6%; 27 W: -15+/-2 and -24+/-6%), with no significant differences between drugs. The major new findings are (1) an exercise-induced intensity-dependent metabolic attenuation of non-adrenergic vasoconstriction in the human leg; and (2) functional evidence that AngII-vasoconstriction is predominantly distal, whereas alpha1-vasoconstriction is proximal and distal within the muscle vascular bed of the human thigh.
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA, and Copenhagen Muscle Research Centre, Department of Cardiology, National Hospital, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark.
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Brothers
authors.forename: Mads L
authors.initials: ML
authors.lastname: Haslund
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.forename: Peter B
authors.initials: PB
authors.lastname: Raven
authors.forename: Mikael
authors.initials: M
authors.lastname: Sander
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology*; D005263:Femoral Artery / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010656:Phenylephrine / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013848:Thigh; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine