Effect of sildenafil, a phosphodiesterase‐5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats

Abstract

The propagation of oesophageal peristaltic contractions and lower oesophageal sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor that increases cGMP, reduces basal LOS pressure in patients with achalasia. We investigated the effect of sildenafil on the propagation of oesophageal contractions and LOS relaxation in the cat. Oesophageal manometry was performed in five cats under light sedation. Peristaltic contractions were monitored at 1, 2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm distal to the upper oesophageal sphincter. Swallow-induced oesophageal contractions and LOS relaxation were recorded during 30 min before and 30 min after intravenous administration of sildenafil. Sildenafil reduced the amplitude of oesophageal contractions only in the smooth muscle oesophagus. The latency from swallow to distal oesophageal contractions was significantly delayed. LOS pressure was significantly reduced but the relaxation nadir was not modified by sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies propagation and amplitude of oesophageal contractions and reduces LOS pressure. Slowing down the propagation of contractions in the transitional zone between the striated and smooth muscle can be a useful tool in patients with segmental aperistalsis or intermittent simultaneous contractions, while the effect on the LOS can benefit patients with achalasia.

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

“…Araujo et al 56 showed that sildenafil had an inhibitory effect on rat duodenal contractility in vitro, which was thought to be caused by a myorelaxant and antispasmodic effect on rat duodenal tissue, most likely secondary to intracellular cGMP accumulation. Almost similar results were shown by Zhang et al 57 in the esophagus of cats by studying the effects of sildenafil propagation of esophageal contractions and lower esophageal sphincter relaxation. The authors concluded that sildenafil caused a reduced amplitude of esophageal contractions.…”

Relevance of ineffective oesophageal motility during oesophageal acid clearance

“…We used sildenafil, a drug known to affect oesophageal motility. [21][22][23][24] Sildenafil had no effect on salivary volume, pH, or buffering capacity suggesting that cGMP has no significant role in human saliva secretion. Sildenafil provoked a gradual reduction in the amplitude of swallow induced peristaltic contractions up to their complete abolition approximately 15 minutes after administration, thereby allowing us to assess the impact of progressive degrees of peristaltic failure during the subsequent clearance tests.…”

A Pilot Study of the Effects of Sildenafil on Stool Characteristics, Colon Transit, Anal Sphincter Function, and Rectal Sensation in Healthy Men

“…On the basis of the known gastrointestinal physiologic effects of NO, modulation of NO signaling may theoretically have a therapeutic role in clinical disorders of the gut. Indeed, previous small studies investigating the gastrointestinal physiological effects of sildenafil, a PDE5 inhibitor (4), in healthy individuals and those with a variety of esophageal motility disorders have demonstrated findings similar to the effects of NO (5)(6)(7)(8)(9)(10). As the influence of PDE inhibition on colonic and anorectal function remains poorly understood, it was our objective to study the effect of sildenafil on stool characteristics, colon transit, anal sphincter function and rectal sensitivity in healthy individuals.…”