Protective Effects of Somatostatin Against Gastric Damage Induced by Hemorrhagic Shock, Stress and PAF in the Rat

Somatostatin is an endogenous cyclic tetradecapeptide which can exert effects on a wide range of gastrointestinal functions, including gastric acid and pepsin secretion, gastric and small intestinal motility, splanchnic blood flow, pancreatic enzyme secretion, intestinal nutrient absorption and gallbladder contractility. Somatostatin has also been shown to reduce the severity of ethanol-induced gastric damage. In this study, we examined the effect of pretreating rats with somatostatin (s.c.) on susceptibility to gastrointestinal damage induced by hemorrhagic shock, stress, platelet-activating factor (PAF), indomethacin or endotoxin. Somatostatin significantly reduced the extent of gastric damage induced by hemorrhagic shock when given at a dose of 20 micrograms/kg or greater (P < 0.05). Somatostatin (20-50 micrograms/kg) also had a dose-dependent protective effect against stress-induced gastric damage. Versus gastric damage induced by intravenous PAF, a dose of 5 micrograms/kg of somatostatin had no effect, while doses of 15-100 micrograms/kg significantly reduced the extent of injury to the stomach. In contrast, somatostatin had no significant effect on gastric or intestinal damage caused by intravenous administration of Salmonella enteritidis endotoxin or by oral administration of indomethacin, despite significantly and dose-dependently (2-10 micrograms/kg) reducing both the volume and titratable acidity of gastric secretion. A protective dose of somatostatin (20 micrograms/kg) had only a small and transient effect on gastric blood flow. The present results demonstrate the effectiveness of somatostatin in protecting the mucosa from injury in a variety of models, and suggest that inhibition of gastric acid secretion is not the sole mechanism underlying these protective effects.