Inhibition of alpha-adrenergic vasoconstriction in exercising human thigh muscles.
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.
Wray
D Walter
DW
Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Fadel
Paul J
PJ
Smith
Michael L
ML
Raven
Peter
P
Sander
Mikael
M
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
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