{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:46:43Z","timestamp":1784101603438,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,2,23]],"date-time":"2004-02-23T00:00:00Z","timestamp":1077494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:p>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 \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoreceptor\u2010mediated vasoconstriction was more sensitive to metabolic inhibition than \u03b1<jats:sub>1<\/jats:sub>\u2010vasoconstriction during dynamic knee\u2010extensor exercise. We studied healthy volunteers using two protocols: (1) wide dose ranges of the \u03b1\u2010adrenoreceptor agonists phenylephrine (PE, \u03b1<jats:sub>1<\/jats:sub>selective) and BHT\u2010933 (BHT, \u03b1<jats:sub>2<\/jats:sub>selective) were administered intra\u2010arterially at rest and during 27 W knee\u2010extensor exercise (<jats:italic>n<\/jats:italic>= 13); (2) flow\u2010adjusted doses of PE (0.3 \u03bcg kg<jats:sup>\u22121<\/jats:sup>l<jats:sup>\u22121<\/jats:sup>) and BHT (15 \u03bcg kg<jats:sup>\u22121<\/jats:sup>l<jats:sup>\u22121<\/jats:sup>) were administered at rest and during ramped exercise (7 W to 37 W;<jats:italic>n<\/jats:italic>= 10). Ultrasound Doppler and thermodilution techniques provided direct measurements of femoral blood flow (FBF). PE (0.8 \u03bcg kg<jats:sup>\u22121<\/jats:sup>) and BHT (40 \u03bcg kg<jats:sup>\u22121<\/jats:sup>) produced comparable maximal reductions in FBF at rest (\u221258 \u00b1 6<jats:italic>versus<\/jats:italic>\u221264 \u00b1 4%). Despite increasing the doses, PE (1.6 \u03bcg kg<jats:sup>\u22121<\/jats:sup>min<jats:sup>\u22121<\/jats:sup>) and BHT (80 \u03bcg kg<jats:sup>\u22121<\/jats:sup>min<jats:sup>\u22121<\/jats:sup>) caused significantly smaller changes in FBF during 27 W exercise (<jats:bold>\u2212<\/jats:bold>13 \u00b1 4<jats:italic>versus<\/jats:italic>\u22123 \u00b1 5%). During ramped exercise, significant vasoconstriction at lower intensities (7 and 17 W) was seen following PE (\u221216 \u00b1 5 and \u221216 \u00b1 4%), but not BHT (\u22122 \u00b1 4 and \u22124 \u00b1 5%). At the highest intensity (37 W), FBF was not significantly changed by either drug. Collectively, these data demonstrate metabolic inhibition of \u03b1\u2010adrenergic vasoconstriction in large postural muscles of healthy humans. Both \u03b1<jats:sub>1<\/jats:sub>\u2010 and \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoreceptor agonists produce comparable vasoconstriction in the resting leg, and dynamic thigh exercise attenuates \u03b1<jats:sub>1<\/jats:sub>\u2010 and \u03b1<jats:sub>2<\/jats:sub>\u2010mediated vasoconstriction similarly. However, \u03b1<jats:sub>2<\/jats:sub>\u2010mediated vasoconstriction appears more sensitive to metabolic inhibition, because \u03b1<jats:sub>2<\/jats:sub>is completely inhibited even at low workloads, whereas \u03b1<jats:sub>1<\/jats:sub>becomes progressively inhibited with increasing workloads.<\/jats:p>","DOI":"10.1113\/jphysiol.2003.054650","type":"journal-article","created":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T01:13:08Z","timestamp":1072746788000},"page":"545-563","source":"Crossref","is-referenced-by-count":72,"title":["Inhibition of \u03b1\u2010adrenergic vasoconstriction in exercising human thigh muscles"],"prefix":"10.1113","volume":"555","author":[{"given":"D. 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