ROLE OF ENDOTHELIN-1 IN REPEATED ELECTRICAL STIMULATION-INDUCED MICROCIRCULATORY DISTURBANCE AND MUCOSAL DAMAGE IN RAT STOMACH

The aim of the present study was to clarify the involvement of endogen ous endothelin in the pathogenesis of gastric mucosal damage. The rat stomach was exposed and repeated electrical stimulation (RES) was appl ied to the small arterial wall close to the lesser curvature. Signific ant mucosal haemorrhagic lesions (ulcer and erosion) were noted within 30 min after RES. Intravital microscopic observations revealed that a n arteriolar constriction occurred in the submucosal layer of the rat stomach approximately 5 min after the completion of RES. Following the arteriolar constriction, the mucosal blood flow of the rat stomach, w hich was monitored by using a laser Doppler velocimeter, decreased to approximately 30% of the control value. The plasma immunoreactive endo thelin-1 level in the regional blood of the stomach was significantly increased immediately after RES preceding the decrease in mucosal bloo d flow Immunohistochemical studies revealed that endothelin-1 and big- endothelin-1 were detectable in the arteriolar endothelium around the muscularis mucosa, supporting the involvement of endothelin-1 in RES-i nduced mucosal ischaemia. In addition, BQ-123, a specific antagonist o f the endothelin A (ET(A)) receptor, attenuated the reduction of blood flow and the development of haemorrhagic lesions observed in gastric mucosa subjected to RES. The results of the present study suggest that an excessive production of endothelin-1 in the arteriolar endothelium leads to microvascular derangements accompanied by haemorrhagic alter ations of the gastric mucosa.