Muscle fibre‐type dependence of neuronal nitric oxide synthase‐mediated vascular control in the rat during high speed treadmill running
Authors: Copp Steven W. , Holdsworth Clark T. , Ferguson Scott K. , Hirai Daniel M. , Poole David C. , Musch Timothy I. 
Published: March 2013

Key points

Neuronal nitric oxide (NO) synthase (nNOS) inhibition does not impact skeletal muscle blood flow or vascular conductance (VC) during low‐speed (20 m min−1) treadmill running.

This may be due to the fact that low exercise intensities recruit primarily oxidative muscle and that nNOS‐derived NO contributes to vascular control primarily within glycolytic muscle.

Rats ran in the severe‐intensity domain at 15% above critical speed (an important glycolytic fast‐twitch fibre recruitment boundary in the rat) before and after selective nNOS inhibition with S‐methyl‐l‐thiocitrulline (SMTC).

SMTC reduced blood flow and VC during supra‐critical speed treadmill running (52.5 ± 1.3 m min−1) with the greatest proportional reductions observed in glycolytic fast‐twitch compared to oxidative slow‐ and fast‐twitch muscle. There were no effects of SMTC on muscle blood flow or VC during low‐speed running (20 m min−1).

The present data reveal important fibre‐type‐ and exercise intensity‐dependent peripheral vascular effects of nNOS‐derived NO during whole‐body exercise.

Abstract  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.