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

Abstract

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 C

Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men

“…Recent evidence in humans (Casey and Joyner 2011) and rodent models (Copp et al 2013) implicate an intensity-dependent role for NO on muscle blood flow responses to exercise (i.e, greater impact of NO synthase blockade at higher intensities), including the rhythmic handgrip exercise model we employed (Wray et al 2011). Our subjects completed 6 steady-state work rates that resulted in a modest ~4-fold increase in forearm blood flow above baseline (Figure 3), but we did not have them exercise at high (i.e., fatiguing) intensities, conditions which would likely have promoted increased activation of the nitrate-nitrite-NO signaling pathway.…”

Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs

“…In addition to these observations in humans and chronically instrumented animals performing voluntary exercise, there is also evidence from a number of sources suggesting that endothelial NO contributes deferentially to the regulation of exercise hyperemia and different fiber types (98). Under some circumstances, fast-twitch skeletal muscle is more dependent on NO-mediated vasodilation than slow-twitch skeletal muscle (100). There are also observations suggesting the opposite pattern of involvement for NO, and this has to do with the exercise intensity and whether the NOS inhibitor was given before or during exercise (334).…”

Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia

“…Further investigations into the NO pathway (neuronal NO synthase (nNOS) and endothelial NO synthase (eNOS)) are required in RSH to determine whether mechanisms other than NO-mediated vasodilation are also involved. Moreover, fibre-type selective peripheral vascular effects of nNOS-derived NO have been reported during high-speed treadmill running, whereas these effects were not seen at slower speeds 89. It is, however, striking to note in two recent studies89 90 a similar fibre-type mechanism on dietary nitrate (NO 3 − ) supplementation that enhances blood flow.…”