Nitric oxide-dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle

Nitric oxide (NO) attenuates α-adrenergic vasoconstriction in contracting rodent skeletal muscle, but it is unclear if NO plays a similar role in human muscle. We therefore hypothesized that in humans, NO produced in exercising skeletal muscle blunts the vasoconstrictor response to sympathetic activation. We assessed vasoconstrictor responses in the microcirculation of human forearm muscle using near-infrared spectroscopy to measure decreases in muscle oxygenation during reflex sympathetic activation evoked by lower body negative pressure (LBNP). Experiments were performed before and after NO synthase inhibition produced by systemic infusion of N^G-nitro-L-arginine methyl ester (L-NAME). Before L-NAME, LBNP at -20 mmHg decreased muscle oxygenation by 20 ± 2 % in resting forearm and by 2 ± 3 % in exercising forearm (n = 20), demonstrating metabolic modulation of sympathetic vasoconstriction. As expected, L-NAME increased mean arterial pressure by 17 ± 3 mmHg, leading to baroreflex-mediated supression of baseline muscle sympathetic nerve activity (SNA). The increment in muscle SNA in response to LBNP at -20 mmHg also was attenuated after L-NAME (before, + 14 ± 2; after, +8 ± 1 bursts min^-1; n = 6), but this effect of L-NAME was counteracted by increasing LBNP to -40 mmHg (+19 ± 2 bursts min^-1). After L-NAME, LBNP at -20 mmHg decreased muscle oxygenation similarly in resting (-11 ± 3 %) and exercising (-10 ± 2 %) forearm (n = 12). Likewise, LBNP at -40 mmHg decreased muscle oxygenation both in resting (-19 ± 4 %) and exercising (-21 ± 5 %) forearm (n = 8). These data advance the hypothesis that NO plays an important role in modulating sympathetic vasoconstriction in the microcirculation of exercising muscle, because such modulation is abrogated by NO synthase inhibition with L-NAME.