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  • Title: Inhibition of alpha-adrenergic vasoconstriction in exercising human thigh muscles.
    Author: Wray DW, Fadel PJ, Smith ML, Raven P, Sander M.
    Journal: J Physiol; 2004 Mar 01; 555(Pt 2):545-63. PubMed ID: 14694145.
    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.
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