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

Abstract 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 (mean ± SD = 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 ) 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. image 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.