Inhibitory Effect of Sildenafil ( Viagra ® ) on Duodenal Motor Activity in Mice

Introduction: Sildenafil citrate (Viagra) is known to relax visceral smooth muscle through the release of neurotransmitter nitric oxide (NO). However, the effect of sildenafil on the structure and motor function of the small intestine has not been fully investigated. Methods: Male Swiss mice were divided into three groups. In the first and second group, animals were treated orally with lowand highdose of sildenafil (2, 4 mg/kg, b.wt., respectively), for 2 weeks. In the third group, sildenafil (30μM) was applied exogenously to the isolated duodenal segment. Physiological and histopathological characteristics were studied and compared to untreated controls. Duodenal motility was assessed using a Trendelenburg preparation to study aboral directed peristaltic motor complexes (PMCs). The contractile activity of the duodenum segment was recorded as changes in intraluminal pressure under isovolumetric conditions. The mean amplitude of PMCs and the frequency (interval) of phasic contractions were determined. Histopathological evaluation was determined using light and scanning electron microscope (SEM). Results: no change in behavior was observed in mice during treatment with lowor highdose of sildenafil (2, 4 mg/kg) compared to control. However, macroscopic analysis showed the finger-shaped of villi in control group which became blunt and flatten in the first group. In the second group, the tip of villi was blunter and broader compared to the first group and control. Microscopical analysis showed minor changes in the first group when compared to control. However, in the second group, there was an increase in eosinophils and worsen intestinal tissue lesions. In submucosal layer, there was an increase in the number of blood vessels and the amount of connective tissue. Hypertrophy and hyperplasia of smooth muscle cells were also observed. Treatment of sildenafil for 2 weeks had no significant changes on motility. Exogenous sildenafil (30μM), significantly decreased PMCs amplitude and increased the interval (P<0.05) compared to control. Conclusion: treatment of male mice with sildenafil for 2 weeks induced structural damage, while exogenous sildenafil produced motor dysfunction of mouse duodenum. [Faiza Abdu and Asma Almuhammadi. Inhibitory Effect of Sildenafil (Viagra) on Duodenal Motor Activity in Mice. Life Sci J 2013; 10(3):1428-1435] (ISSN: 1097-8135).http://www.lifesciencesite.com. 214