Gastric ulcer has become a global problem with increasing incidence and prevalence; implicated by emotional and physical stresses. It has been shown that stress exposure impedes the gastric and duodenal defences against the damage induced by an attack from acid and pepsin damage. Resultant local mechanisms leading to the breakdown of the gastro duodenal mucosal barrier include reduced mucosal blood flow, decreased local bicarbonate secretion, increased acid back-diffusion, and decreased GI motility. The gastric barrier protects the mucosa against damage of its deeper structures by noxious substances. Mucosal microcirculation of the stomach has an important role in gastric mucosal protection. Prostaglandins and NO are the main factors that regulate gastric blood flow. Possible mechanisms of gastro-protection of PDE V inhibitors are increased production of tissue NO or increased tissue cGMP level without modifying NO content.