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

Abstract

Key pointsr At rest, dopamine induces recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) and increases venous admixture (i.e.Q s /Q t ).r Dopamine increases during exercise, and may be partly responsible for exercise-induced IPAVA recruitment.r In this study, we antagonized dopamine receptors with metoclopramide, and observed improved pulmonary gas exchange but no difference in IPAVA recruitment during exercise.r Dopamine blockade decreased cardiac output at peak exercise, resulting in decreased exercise performance.r Increasing endogenous dopamine is important for the normal healthy response to exercise. Abstract Pulmonary gas exchange, as evaluated by the alveolar-arterial oxygen difference (A-aD O 2 ), 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-aD O 2 and IPAVA recruitment would be decreased with DA receptor blockade. Twelve healthy males (age: 25 ± 6 years,V O 2 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% ofV O 2 max . On different days, participants also completed incremental exercise tests and exercise tolerance (time-to-exhaustion (TTE) at 85% ofV O 2 max ) with or without dopamine blockade. Compared to placebo, DA blockade did not change O 2 consumption, CO 2 production, or respiratory exchange ratio at any intensity. At 85%V O 2 max , DA blockade decreased A-aD O 2 , increased arterial O 2 saturation and minute ventilation, but did not reduce IPAVA recruitment, suggesting that positive saline contrast is unrelated to A-aD O 2 . Compared to placebo, DA blockade decreased maximal cardiac output,V O 2 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.

The effect of dopamine on pulmonary diffusing capacity and capillary blood volume responses to exercise in young healthy humans

“…These studies showed that dopamine receptor agonists improve exercise tolerance only under conditions of thermal stress (Roelands et al., ; Watson et al., ). Consistent with work in humans (Tedjasaputra et al., ) and animals (Balthazar, Leite, Ribeiro, Soares, & Coimbra, ), dopamine receptor blockade reduced exercise tolerance. In our previous work, the reduction in time‐to‐exhaustion with dopamine blockade was explained in part by a reduction in and stroke volume (Tedjasaputra et al., ).…”

“…Consistent with work in humans (Tedjasaputra et al., ) and animals (Balthazar, Leite, Ribeiro, Soares, & Coimbra, ), dopamine receptor blockade reduced exercise tolerance. In our previous work, the reduction in time‐to‐exhaustion with dopamine blockade was explained in part by a reduction in and stroke volume (Tedjasaputra et al., ). However, in the current study, we did not find any change in stroke volume or with D 2 ‐receptor blockade.…”

“…To our knowledge, there is no previous work measuring the effect of exogenous dopamine on pulmonary diffusing capacity, and thus there was no reference to calculate an effect size of dopamine modulation on DL CO , V c or D m . However, data from our previous work (Tedjasaputra et al., ) indicated that a sample size of 13 would be sufficient to detect a significant reduction in time‐to‐exhaustion with D 2 ‐receptor blockade (desired power level of 0.80, α = 0.05). Subjects were physically active non‐smokers with normal lung function.…”

“…Consistent with previous work, DL CO increased during exercise secondary to increases in V c and D m (Bouwsema et al., ; Hsia, ; Tedjasaputra et al., ). Animal studies have shown direct evidence that dopamine is a pulmonary vasodilator (Hoshino et al., ; Polak et al., ) and human studies suggest that dopamine plays a role in pulmonary vasculature regulation (Bryan et al., ; Tedjasaputra et al., ). During exercise, there is a natural rise in endogenous levels of circulating dopamine (Hopkins et al., ).…”

Precapillary pulmonary gas exchange is similar for oxygen and inert gases

“…In addition, the coefficient of variations for (1.6%) and (2.2%) were small, and similar to values seen following immediate analysis using the same blood gas analyser (Tedjasaputra et al . ), suggesting no additional variance as would have been expected from inadvertent bubble contamination.…”