Dopamine receptor blockade improves pulmonary gas exchange but decreases exercise performance in healthy humans

Abstract

Key points: At rest, dopamine induces recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) and increases venous admixture (i.e. Q˙s/Q˙t). Dopamine increases during exercise, and may be partly responsible for exercise-induced IPAVA recruitment. In this study, we antagonized dopamine receptors with metoclopramide, and observed improved pulmonary gas exchange but no difference in IPAVA recruitment during exercise. Dopamine blockade decreased cardiac output at peak exercise, resulting in decreased exercise performance. Increasing endogenous dopamine is important for the normal healthy response to exercise. Pulmonary gas exchange, as evaluated by the alveolar-arterial oxygen difference (A-aDO2), is impaired during intense exercise, and has been correlated with recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) as measured by agitated saline contrast echocardiography. Previous work has shown that dopamine (DA) recruits IPAVA and increases venous admixture (Q˙s/Q˙t) at rest. As circulating DA increases during exercise, we hypothesized that A-aDO2 and IPAVA recruitment would be decreased with DA receptor blockade. Twelve healthy males (age: 25 ± 6 years, V˙O2 max : 58.6 ± 6.5 ml kg-1 min-1) performed two incremental staged cycling exercise sessions after ingestion of either placebo or a DA receptor blocker (metoclopramide 20 mg). Arterial blood gas, cardiorespiratory and IPAVA recruitment (evaluated by agitated saline contrast echocardiography) data were obtained at rest and during exercise up to 85% of V˙O2 max. On different days, participants also completed incremental exercise tests and exercise tolerance (time-to-exhaustion (TTE) at 85% of V˙O2 max) with or without dopamine blockade. Compared to placebo, DA blockade did not change O2 consumption, CO2 production, or respiratory exchange ratio at any intensity. At 85% V˙O2 max , DA blockade decreased A-aDO2, increased arterial O2 saturation and minute ventilation, but did not reduce IPAVA recruitment, suggesting that positive saline contrast is unrelated to A-aDO2. Compared to placebo, DA blockade decreased maximal cardiac output, V˙O2 max and TTE. Despite improving pulmonary gas exchange, blocking dopamine receptors appears to be detrimental to exercise performance. These findings suggest that endogenous dopamine is important to the normal cardiopulmonary response to exercise and is necessary for optimal high-intensity exercise performance.