title: Inhibition of alpha-adrenergic vasoconstriction in exercising human thigh muscles.
abstract: The mechanisms underlying metabolic inhibition of sympathetic responses within exercising skeletal muscle remain incompletely understood. The aim of the present study was to test whether alpha(2)-adrenoreceptor-mediated vasoconstriction was more sensitive to metabolic inhibition than alpha(1)-vasoconstriction during dynamic knee-extensor exercise. We studied healthy volunteers using two protocols: (1) wide dose ranges of the alpha-adrenoreceptor agonists phenylephrine (PE, alpha(1) selective) and BHT-933 (BHT, alpha(2) selective) were administered intra-arterially at rest and during 27 W knee-extensor exercise (n= 13); (2) flow-adjusted doses of PE (0.3 microg kg(-1) l(-1)) and BHT (15 microg kg(-1) l(-1)) were administered at rest and during ramped exercise (7 W to 37 W; n= 10). Ultrasound Doppler and thermodilution techniques provided direct measurements of femoral blood flow (FBF). PE (0.8 microg kg(-1)) and BHT (40 microg kg(-1)) produced comparable maximal reductions in FBF at rest (-58 +/- 6 versus-64 +/- 4%). Despite increasing the doses, PE (1.6 microg kg(-1) min(-1)) and BHT (80 microg kg(-1) min(-1)) caused significantly smaller changes in FBF during 27 W exercise (-13 +/- 4 versus-3 +/- 5%). During ramped exercise, significant vasoconstriction at lower intensities (7 and 17 W) was seen following PE (-16 +/- 5 and -16 +/- 4%), but not BHT (-2 +/- 4 and -4 +/- 5%). At the highest intensity (37 W), FBF was not significantly changed by either drug. Collectively, these data demonstrate metabolic inhibition of alpha-adrenergic vasoconstriction in large postural muscles of healthy humans. Both alpha(1)- and alpha(2)-adrenoreceptor agonists produce comparable vasoconstriction in the resting leg, and dynamic thigh exercise attenuates alpha(1)- and alpha(2)-mediated vasoconstriction similarly. However, alpha(2)-mediated vasoconstriction appears more sensitive to metabolic inhibition, because alpha(2) is completely inhibited even at low workloads, whereas alpha(1) becomes progressively inhibited with increasing workloads.
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fadel
authors.forename: Michael L
authors.initials: ML
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Raven
authors.forename: Mikael
authors.initials: M
authors.lastname: Sander
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000465:Algorithms; D001381:Azepines / Q000494:pharmacology; D002406:Catheterization, Peripheral; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D013815:Thermodilution; D013848:Thigh / Q000000981:diagnostic imaging / Q000502:physiology; D014463:Ultrasonography; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001381:Azepines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D015016:Yohimbine; D011433:Propranolol; C015603:azepexole