No Acute Effect Of Phosphodiesterase-5 Inhibition On Pulmonary Oxygen Uptake Kinetics At The Onset Of Moderate-Intensity Exercise In Trained And Untrained Adults

Abstract

The nitric oxide (NO)-3′5′cyclic guanosine monophosphate (cGMP) signaling pathway has been implicated in the regulation of muscle vasodilatation as well as oxidative metabolism during exercise. Inhibition of Phosphodiesterase-5 reduces cGMP hydrolysis and might, to some extent, influence muscle hemodynamic and oxidative processes, and arguably, affect pulmonary oxygen uptake kinetics during exercise. PURPOSE: To test the hypothesis that acute administration of Tadalafil, a phosphodiesterase-5 inhibitor commonly used for therapeutic purposes, speeds pulmonary oxygen uptake kinetics at the onset of moderate-intensity exercise in trained and untrained adults. METHODS: Six untrained (mean age 23.3 ± 3.2 yr, VO2 peak 2996 ± 239 mL.min-1) and six trained (mean age 22.3 ± 1.0 yr, VO2 peak 3279 ± 353 mL.min-1) males were assigned in a randomized, double-blind, crossover design to receive either one tablet of placebo or Tadalafil (20mg), with a 7 d washout period in between. Subjects completed square-wave transitions to power outputs requiring 80% of gas exchange threshold (GET) from a baseline of unloaded cycling. Pulmonary oxygen uptake was measured breath-by-breath and individual responses were modeled using nonlinear regression techniques. Data were analyzed using repeated measures ANOVA and unpaired t tests (P < 0.05). RESULTS: The VO2 time constant was slower (P < 0.05) in the untrained compared with the trained subjects in both placebo (42 ± 14 s vs 29 ± 5 s) and Tadalafil (42 ± 15 s vs 29 ± 14 s) conditions, respectively, but unaffected by the drug ingestion. The time delay was similar in untrained and trained subjects for placebo (24 ± 7 s and 20 ± 5 s), but not for Tadalafil (28 ± 7 s and 11 ± 5 s; P < 0.05) condition, respectively; however, the time delay was also unaffected by the drug ingestion. The VO2 amplitude was smaller (P < 0.05) in the untrained compared with the trained subjects in both placebo (1285 ± 230 s vs 1755 ± 305 s) and Tadalafil (1238 ± 187 s vs 1674 ± 232 s) conditions, respectively, but unaffected by the drug ingestion. The heart rate (HR) time constant was similar in trained and untrained subjects for both placebo (42 ± 8 s and 38 ± 12 s) and Tadalafil (30 ± 12 s and 36 ± 8 s) conditions, respectively, and did not differ between the two conditions. CONCLUSION: Inhibition of Phospodiesterase-5 did not alter pulmonary oxygen uptake kinetics at the onset of moderate-intensity exercise in healthy adults, regardless of training status.