title: Blunted sympathetic vasoconstriction in contracting skeletal muscle of healthy humans: is nitric oxide obligatory?
abstract: We tested the hypothesis that nitric oxide (NO) is responsible for blunting sympathetic alpha-adrenergic vasoconstriction in the active muscles of humans (functional sympatholysis). We measured forearm blood flow (Doppler ultrasound) and calculated the reductions in forearm vascular conductance (FVC) in response to alpha-adrenergic receptor stimulation during rhythmic handgrip exercise and during a control non-exercise vasodilator condition (intra-arterial adenosine), before and after local NO synthase (NOS) inhibition in healthy men. The forearm vasoconstrictor responses to endogenous noradrenaline release (intra-arterial tyramine) were significantly blunted during moderate exercise compared with adenosine, and these vasoconstrictor responses were not restored by NOS inhibition with NG-monomethyl-L-arginine (L-NMMA; n = 6) or NG-nitro-L-arginine methyl ester (L-NAME; n = 8). Similarly, L-NAME did not restore the vasoconstrictor responses to tyramine in contracting muscle during heavy rhythmic handgrip exercise (n = 4). In four additional subjects, we also found that the vasoconstrictor responses evoked by tyramine during exercise or adenosine were repeatable in the absence of NOS inhibition (i.e. time control). Finally, in five subjects the forearm vasoconstrictor responses to direct alpha 1-adrenergic (phenylephrine) and alpha 2-adrenergic (clonidine) receptor stimulation were blunted during moderate exercise compared with adenosine; these responses were also unaffected by L-NAME. Taken together, our results demonstrate that NO is not obligatory for functional sympatholysis in contracting skeletal muscles of healthy men.
authors.affiliation: Department of Anesthesiology and General Clinical Research Center, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Dinenno
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D018737:Hand Strength; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000241:Adenosine; D014439:Tyramine