Attenuation of Cold Restraint Stress-Induced Gastric Lesions by Sildenafil in Rats

Aim: To investigate the protective effect of sildenafil citrate, a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase, on gastric mucosal damage induced by cold restraint stress (CRS) in rats. Further, the study was extended to investigate some possible mechanisms underlying this effect. Material and Methods: Forty rats were randomly divided into 4 groups. Normal control, CRS group, rats received saline restrained and maintained at 4°C for 3h., sildenafil group rats received sildenafil (10mg/kg, p.o.) 30min Before CRS and fourth group received L-NAME 15min. Before+sildenafil before CRS. Results: The results indicated that cold stress induced marked ulceration in the gastric mucosa, in addition to an increase in gastric acidity as compared to saline group (p•0.05). Furthermore, stress showed reduced glutathione, whereas lipid peroxides were elevated in the stomach homogenate. Pretreatment with sildenafil (10mg/kg p.o.) significantly reduced ulcer index, gastric muscosal malondialdehyde concentration compared with CRS without treatment rats. On the other hand, sildenafil (10mg/kg p.o.) provided increasing tissue NO (p•0.05). On the other hand, Pretreatment with LNAME [N (G)-nitro-L-arginine methyl ester], a NO synthase inhibitor, partly altered the protection showed by sildenafil. Conclusion: The present work concluded that sildenafil can protect the gastric mucosa against the aggressive effect of cold stress via increasing NO and inhibiting lipid peroxidation. Therefore, sildenafil might be helpful in preventing the gastric adverse effects of stress induced ulcer in a clinical setting.