Role of endothelin in the pathogenesis of gastric mucosal hemorrhagic lesion.

Microcirculatory distrubances are thought to be a cruicial step for the development of hemorrhagic changes in the gastric mucosa. In recent years, the interest in the pathophysiological role of endothelin has increased considerably. Nevertheless the influence of endothelin in gastric microcirculation has not been fully demonstrated. In this study, we investigated the role of endothelin in the process of gastric microcirculatory derangement followed by the mucosal damage. The stomach of male Wistar rat (200 g) was used in this study. Endothelin-1 was injected into the SCA to give final concentrations of 50-500 pmol/kg. Endothelin-induced microvascular changes in the submucosal layer were visualized through a SIT camera. The mucosal blood flow was also monitored using a laser doppler flowmeter. Thirty minutes after the injection of endothelin-1, the stomach was opened for estimating hemorrhagic lesion and histological changes. Endothelin-1 caused a sustained microvascular constriction and subsequent decrease in mucosal blood flow. This constrictive change was enhanced in the terminal arteriole. Thirty minutes after the administration, the mucosal lesion occured in a dose-dependent manner of endothelin-1. In conclusion, the present study revealed that the constrictive change in the terminal arteriole may be important in the developement of endothelin-induced gastric mucosal damage.