Muscle fibre-type dependence of neuronal nitric oxide synthase-mediated vascular control in the rat during high speed treadmill running

J Physiol. 2013 Jun 1;591(11):2885-96. doi: 10.1113/jphysiol.2013.251082. Epub 2013 Mar 18.


We have recently shown that nitric oxide (NO) derived from neuronal NO synthase (nNOS) does not contribute to the hyperaemic response within rat hindlimb skeletal muscle during low-speed treadmill running. This may be attributed to low exercise intensities recruiting primarily oxidative muscle and that vascular effects of nNOS-derived NO are manifest principally within glycolytic muscle. We tested the hypothesis that selective nNOS inhibition via S-methyl-l-thiocitrulline (SMTC) would reduce rat hindlimb skeletal muscle blood flow and vascular conductance (VC) during high-speed treadmill running above critical speed (asymptote of the hyperbolic speed versus time-to-exhaustion relationship for high-speed running and an important glycolytic fast-twitch fibre recruitment boundary in the rat) principally within glycolytic fast-twitch muscle. Six rats performed three high-speed treadmill runs to exhaustion to determine critical speed. Subsequently, hindlimb skeletal muscle blood flow (radiolabelled microspheres) and VC (blood flow/mean arterial pressure) were determined during supra-critical speed treadmill running (critical speed + 15%, 52.5 ± 1.3 m min(-1)) before (control) and after selective nNOS inhibition with 0.56 mg kg(-1) SMTC. SMTC reduced total hindlimb skeletal muscle blood flow (control: 241 ± 23, SMTC: 204 ± 13 ml min(-1) (100 g)(-1), P < 0.05) and VC (control: 1.88 ± 0.20, SMTC: 1.48 ± 0.13 ml min(-1) (100 g)(-1) mmHg(-1), P < 0.05) during high-speed running. The relative reductions in blood flow and VC were greater in the highly glycolytic muscles and muscle parts consisting of 100% type IIb+d/x fibres compared to the highly oxidative muscles and muscle parts consisting of 35% type IIb+d/x muscle fibres (P < 0.05). These results extend our understanding of vascular control during exercise by identifying fibre-type-selective peripheral vascular effects of nNOS-derived NO during high-speed treadmill running.

MeSH terms

  • Animals
  • Arterial Pressure
  • Glycolysis
  • Hindlimb / blood supply
  • Male
  • Muscle Fibers, Fast-Twitch / classification
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscle, Skeletal / blood supply*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / metabolism*
  • Oxidative Phosphorylation
  • Physical Exertion*
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow
  • Running


  • Nitric Oxide
  • Nitric Oxide Synthase Type I