Metabolic modulation of sympathetic vasoconstriction in human skeletal muscle: Role of tissue hypoxia

1. Sympathetically evoked vasoconstriction is modulated by skeletal muscle contraction, but the underlying events are incompletely understood. During contraction, intramuscular oxygenation decreases with increasing exercise intensity. We therefore hypothesized that tissue hypoxia plays a crucial role in the attenuation of sympathetic vasoconstriction in contracting skeletal muscle. 2. In 19 subjects, near-infrared spectroscopy was used to measure decreases in muscle oxygenation (ΔtHbO₂ + MbO₂) as an estimate of the vasoconstrictor response to reflex sympathetic activation with lower body negative pressure (LBNP) in the microcirculation of resting and contracting forearm muscles. Oxygen delivery to the muscles was reduced by decreasing (a) arterial O₂ content by breathing 10% O₂, or (b) muscle perfusion by applying forearm positive pressure (FPP, +40 mmHg). 3. In resting forearm, reflex sympathetic activation decreased muscle oxygenation by 11 ± 1%. Handgrip alone at 5 and 20% of maximal voluntary contraction (MVC) decreased muscle oxygenation by 4 ± 1 and 28 ± 4%, respectively. When superimposed on handgrip, LBNP-induced decreases in muscle oxygenation were preserved during handgrip at 5% MVC, but were abolished during handgrip at 20% MVC. Oral administration of aspirin (1 g) did not restore the latter response. 4. When the decrease in forearm muscle oxygenation elicited by handgrip at 20% MVC was mimicked by either (a) systemic hypoxia plus 5% handgrip (ΔtHbO₂ + MbO₂, -32 ± 3%), or (b) hypoperfusion of resting muscle by FPP (ΔtHbO₂ + MbO₂, -26 ± 6%), LBNP-induced decreases in muscle oxygenation were greatly attenuated. 5. These data suggest that local tissue hypoxia is involved in the metabolic attenuation of sympathetic vasconstriction in the microcirculation of exercising human skeletal muscle. The specific underlying mechanism remains to be determined, although products of the cyclo-oxygenase pathway do not appear to be involved.