Elevation of gastric blood flow as the mechanism of antiulcer effects of Pro-Gly-Pro

Abstract

Subcutaneous injection of indomethacin to pentobarbital-anesthetized rats markedly reduced gastric blood flow measured by hydrogen clearance method in the antrum and fundus of the stomach. Intraperitoneal injection of Pro-Gly-Pro 10 min after the administration of indomethacin normalized gastric blood flow. These data indicate that the elevation of reduced regional blood flow in the stomach is one of possible mechanisms of antiulcer effects of ProGly-Pro. Key Words: gastric blood flow; indomethacin; proline-containing oligopeptidesRecent data indicate that oligopeptides containing proline and glycine posses various biological activities [3]. Protective effects of proline-containing peptides, in particular of Pro-Gly-Pro (PGP), on the gastric mucosa (GM) were demonstrated on various experimental models of ulcer formation mediated by central and peripheral mechanisms [ 1]. For example, PGP attenuates GM injuries induced by indomethacin (IM) [1], which are primarily related to the peripheral factors impairing protective mechanisms. For-instance, inhibition of prostaglandin synthesis suppresses mucus secretion and cell regeneration and reduces blood flow [6].However, the mechanisms of antiulcer effects of PGP are poorly understood. Previous experiments showed that PGP attenuates the effect of aggressive factors, in particular, it inhibits secretion of hydrochloric acid [2]. It was proposed that PGP stimulates protective mechanisms. Studies of vascular resistance under conditions of perfusion of the posterior part of rat body revealed vasodilating properties of this peptide. It is well known that changes in gastric blood flow do not necessarily correspond to systemic blood pressure fluctuations. Blood flow in GM remains unchanged during considerable fluctuations of systemic blood pressure, and vice versa [7,8].Here we evaluated the effects of PGP on IM-induced reduction of GM blood flow in narcotized rats.