The effect of sildenafil on resting and exercise diffusing capacity in trained and untrained individuals: A randomized crossover trial

Higher pulmonary microvascular function may contribute to higher rest and exercise diffusing capacity (DLCO), pulmonary capillary blood volume (VC) and membrane diffusing capacity (DM) in trained individuals. We hypothesized that pulmonary vasodilatation with sildenafil would increase resting and exercise DLCO, VC and DM in untrained (UT) individuals, whereas trained (T) individuals would have a smaller response. This double-blind randomized crossover trial recruited n = 24 healthy participants (nine females) into UT and T groups (n = 12 each) based on V̇O2peak (mean ± SD V̇O2peak = 37.5 ± 3.8 and 65.3 ± 6.7 mL.kg-1 .min-1, respectively). Rest and exercise DLCO (cycle ergometry; 60 W, 30%, 60% and 90% of V̇O2peak) was measured following oral sildenafil (50 mg) or placebo (block randomized) and evaluated using one-way ANOVA and linear mixed effects modelling. At rest, right ventricular systolic pressure was reduced with sildenafil across groups (mean ∆ = -2.1 mmHg; P = 0.01), indicating effective pulmonary vasodilatation. No group, drug or drug by group interaction effect was detected in resting DLCO, VC or DM (all Pgroup > 0.058). T had higher exercise DLCO during all workloads (all Pgroup C in relative workloads (Pgroup = 0.006). Sildenafil did not impact exercise DLCO, VC or DM at any workload (all Pdrug > 0.395), with no significant drug by group interaction (all Pinteraction > 0.086). As sildenafil did not impact rest or exercise DLCO, VC or DM in either group, there was no evidence that improved nitric oxide-mediated pulmonary vasodilatory function would explain the greater DLCO observed in trained individuals. KEY POINTS: Higher pulmonary vascular function may explain why trained individuals have higher pulmonary diffusing capacity for carbon monoxide (DLCO) compared to untrained individuals. This double-blind randomized crossover trial investigated whether pulmonary vasodilatation with sildenafil would elucidate changes in resting and exercise DLCO within trained and untrained groups. Trained individuals had higher DLCO, but sildenafil did not elicit alterations in DLCO in either group. Our findings suggest that improved nitric oxide-mediated pulmonary vasodilatation is not likely the primary mechanism responsible for the greater DLCO observed in trained individuals. Future work should investigate which mechanism(s) are responsible for the higher DLCO in trained individuals.