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

Higher pulmonary microvascular function may contribute to higher rest and exercise diffusing capacity (DL_CO), pulmonary capillary blood volume (V_C) and membrane diffusing capacity (D_M) in trained individuals. We hypothesized that pulmonary vasodilatation with sildenafil would increase resting and exercise DL_CO, V_C and D_M 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 $\dot{V}{O}_{2\mathrm{peak}}$ (mean ± SD $\dot{V}{O}_{2\mathrm{peak}}$ = 37.5 ± 3.8 and 65.3 ± 6.7 mL^.kg^{-1 .}min^-1, respectively). Rest and exercise DL_CO (cycle ergometry; 60 W, 30%, 60% and 90% of $\dot{V}{O}_{2\mathrm{peak}}$ ) 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 DL_CO, V_C or D_M (all P_group > 0.058). T had higher exercise DL_CO during all workloads (all P_group < 0.031) and higher V_C in relative workloads (P_group = 0.006). Sildenafil did not impact exercise DL_CO, V_C or D_M at any workload (all P_drug > 0.395), with no significant drug by group interaction (all P_interaction > 0.086). As sildenafil did not impact rest or exercise DL_CO, V_C or D_M in either group, there was no evidence that improved nitric oxide-mediated pulmonary vasodilatory function would explain the greater DL_CO observed in trained individuals. KEY POINTS: Higher pulmonary vascular function may explain why trained individuals have higher pulmonary diffusing capacity for carbon monoxide (DL_CO) compared to untrained individuals. This double-blind randomized crossover trial investigated whether pulmonary vasodilatation with sildenafil would elucidate changes in resting and exercise DL_CO within trained and untrained groups. Trained individuals had higher DL_CO, but sildenafil did not elicit alterations in DL_CO in either group. Our findings suggest that improved nitric oxide-mediated pulmonary vasodilatation is not likely the primary mechanism responsible for the greater DL_CO observed in trained individuals. Future work should investigate which mechanism(s) are responsible for the higher DL_CO in trained individuals.