PDE5 inhibitors for cystic fibrosis: can they also enhance chloride transport?

Evaluation of: Lubamba B, Lecourt H, Lebacq J, et al. Preclinical evidence that sildenafi l and vardenafi l activate chloride transport in cystic fi brosis. Am J Respir Crit Care Med 2008;177(5):506–15

Background: Many compounds are currently under investigation for cystic fibrosis (CF), a genetic disorder caused by various mutations in cystic fibrosis transmembrane regulator (CFTR). Objective: To evaluate a preclinical study on the effects of sildenafil and vardenafil, two PDE5 inhibitors, on ion transport in CF animal models. Methods/results: The effects of sildenafil and vardenafil on chloride and sodium conductance were assessed in both ΔF508CFTR and CFTR knockout mice models. They improved chloride transport in the ΔF508CFTR model and had no effects in the CFTR knockout model. Conclusion: Sildenafil and vardenafil are promising agents for CF therapy provided they also demonstrate clinical efficacy.