Inhibition of α-adrenergic vasoconstriction in exercising human thigh muscles

D. Walter Wray, Paul J. Fadel, Michael L. Smith, Peter Raven, Mikael Sander

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


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 α2-adrenoreceptor-mediated vasoconstriction was more sensitive to metabolic inhibition than α1-vasoconstriction during dynamic knee-extensor exercise. We studied healthy volunteers using two protocols: (1) wide dose ranges of the α-adrenoreceptor agonists phenylephrine (PE, α1 selective) and BHT-933 (BHT, α2 selective) were administered intra-arterially at rest and during 27 W knee-extensor exercise (n = 13); (2) flow-adjusted doses of PE (0.3 μg kg-1 l-1) and BHT (15 μg 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 μg kg-1) and BHT (40 μg kg-1) produced comparable maximal reductions in FBF at rest (-58 ± 6 versus -64 ± 4%). Despite increasing the doses, PE (1.6 μg kg-1 min-1) and BHT (80 μg 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 α-adrenergic vasoconstriction in large postural muscles of healthy humans. Both α1- and α2-adrenoreceptor agonists produce comparable vasoconstriction in the resting leg, and dynamic thigh exercise attenuates α1- and α2-mediated vasoconstriction similarly. However, α2-mediated vasoconstriction appears more sensitive to metabolic inhibition, because α2 is completely inhibited even at low workloads, whereas α1 becomes progressively inhibited with increasing workloads.

Original languageEnglish
Pages (from-to)545-563
Number of pages19
JournalJournal of Physiology
Issue number2
StatePublished - 1 Mar 2004


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