Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders

Background and aims: Sildenafil blocks phosphodiesterase type 5 which degrades nitric oxide (NO) stimulated 3'5'-cyclic monophosphate (cGMP), thereby relaxing smooth muscle cells in various organs. We used sildenafil as a tool to investigate the role of the NO-cGMP pathway in the oesophagus of healthy volunteers and patients with hypercontractile oesophageal motility disorders. Methods: Six healthy male volunteers participated in a randomised double blind study on two separate days before and one hour after oral intake of either sildencifil 50 mg or placebo. Oesophageal manometry was performed to determine vector volume of the lower oesophageal sphincter (LOS) and pressure amplitudes of the oesophageal body. Four of the volunteers underwent 12 hour ambulatory oesophageal manometry on two separate days, once with sildenafil 50 mg and once with placebo. An activity index for spontaneous swallowing was calculated for every hour of the study. Eleven patients with hypercontractile oesophageal motility disorders took part in an open study of the effect of 50 mg sildenafil on manometric features of their disorder and on the clinical response to sildenafil taken as required. Results: In healthy subjects, sildenafil significantly reduced LOS pressure vector volume and pressure amplitudes in the distal half of the oesophageal body. In three of four subjects the inhibitory effect of sildenafil lasted at least eight hours. In nine of I I patients, manometric improvement after sildenafil was observed but only four had an improvement in oesophageal symptoms with sildenafil taken as required. Two of these four patients however experienced side effects and did not want to continue treatment. Conclusions: Sildenafil lowers LOS pressure and propulsive forces in the body of the oesophagus of healthy subjects as well as in patients with nutcracker oesophagus, hypertensive LOS, and achalasia. The effect of sildenafil on the oesophageal body may last for up to eight hours in healthy volunteers. A subset of patients with hypertensive LOS or nutcracker oesophagus may benefit from sildenafil but side effects are a limiting factor.