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 article

61 Scopus citations

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 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
Volume555
Issue number2
DOIs
StatePublished - 1 Mar 2004

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