Inhibitory Effects of Sildenafil on Small Intestinal Motility and Myoelectrical Activity in Dogs

Abstract

Previous studies have shown that sildenafil inhibits the esophageal motility in both humans and animals. The aim of this study was to investigate the effects of sildenafil on intestinal myoelectrical activity and motility. The study was composed of 2 experiments and performed in 7 healthy female dogs with a duodenal cannula 20 cm beyond pylorus (19-26 kg). The first experiment was designed to study the effects of sildenafil on intestinal myoelectrical activity and it included 2 sessions each consisting of 30-minute baseline, 15-minute posttreatment (placebo or 100 mg sildenafil) and 90 minutes after a liquid meal. Intestinal myoelectrical activity was recorded during the entire experiment period. The second experiment was aimed to investigate the effect of sildenafil on intestinal motility and was performed immediately after a solid meal. Intestinal motility was measured by a manometric catheter inserted into the small intestine via the duodenum cannula for 30 minutes at baseline and 60 minutes after sildenafil. Sildenafil significantly reduced the amplitude but had no effect on the frequency and regularity of the intestinal myoelectrical activity. Sildenafil significantly inhibited postprandial intestinal contractions. Although the frequency of the contractions was not altered, the mean area under the curve was significantly reduced during the first 30 minutes (P < .03) and second 30 minutes after sildenafil (P < .03); the power of intestinal contractile activities was also significantly reduced during the first 30 minutes (P < .0004) and second 30 minutes after sildenafil (P < .0003) in comparison with baseline. In conclusion, sildenafil inhibits the amplitude of both intestinal contractile activity and intestinal slow waves.

Sildenafil normalizes bowel transit in preclinical models of constipation

“…Sildenafil is absorbed systemically and has well-established relaxation effects on smooth muscle that might affect transit. Several studies have reported a reduction in esophageal contractile force by sildenafil treatment, particularly in patients with dysmotility disorders, but this effect is less pronounced in the normal esophagus and in the lower intestine [38,39,40,41,42]. Reduced muscular contractility cannot explain the results reported here because this would be expected to further increase transit time in our disease models, but as shown here, sildenafil reduced transit time.…”

Inhibitory effects of sildenafil on gastric motility and gastric slow waves in dogs

“…The dominant power of the gastric slow wave has been associated with the contractility of the stomach; an increase in the dominant power of the gastric slow wave was reported to be accompanied with an increase in gastric motility and vice versa 29,31 . In a separate study, we investigated the effects of sildenafil on intestinal slow waves 32 and found that sildenafil significantly reduced the amplitude but not the frequency or regularity of the intestinal myoelectrical activity.…”