Functional Sympatholysis: Integrated Vascular Regulation in Active Skeletal Muscle
Recent studies indicate that skeletal muscle-derived nitric oxide (NO) plays an important role in attenuating sympathetically-mediated vasoconstriction in exercising muscle (i.e., functional sympatholysis). Because superoxide can rapidly react with and inactivate NO, we hypothesized that the normal attenuation of sympathetic vasoconstriction in exercising muscle would be impaired during nitrate tolerance, a condition known to increase superoxide production. To begin to test this hypothesis, experiments were performed in healthy subjects before and after nitrate tolerance produced by three days of continuous exposure to transdermal nitroglycerin (0.5 mg/hr). Vasoconstrictor responses in the microcirculation of resting and exercising forearm muscle were assessed using near infrared spectroscopy to measure decreases in muscle oxygenation during reflex sympathetic activation evoked by lower body negative pressure (LBNP) at −20 mmHg. Before nitrate tolerance, LBNP induced decreases in muscle oxygenation were attenuated during rhythmic handgrip compared to rest demonstrating functional sympatholysis. However, after the development of nitrate tolerance LBNP induced similar decreases in muscle oxygenation at rest and during exercise indicating impaired functional sympatholysis. As expected, functional sympatholysis was restored after recovery from nitrate tolerance. These preliminary data suggest that nitrate tolerance impairs the modulation of sympathetic vasoconstriction in exercising muscle perhaps by increasing superoxide production leading to decreased bioavailability of NO. Supported by NIH grant HL06296.