ROLE OF ENDOGENOUS ENDOTHELIN IN GASTRIC-MUCOSAL INJURY-INDUCED BY HEMORRHAGIC-SHOCK IN RATS

We examined the role of endogenous endothelin in the pathogenesis of h emorrhagic shock-induced gastric mucosal injury in rats. Animals were bled to induce hypotension (20-30 mm Hg) for 20 min and the shed blood was retransfused. Rats were sacrificed at the end of hypotension, 20 min, and 60 min after retransfusion, respectively. Gastric erosions we re induced with this experimental protocol. The total area of erosions was minimal only at the end of hypotension, and increased time-depend ently after blood retransfusion. Plasma endothelin concentration signi ficantly increased at the end of hypotension and persistently increase d after retransfusion, whereas in gastric endothelin concentration a s ignificant increase was observed at 60 min after retransfusion. The ga stric mucosal hemodynamics as assessed by continuous measurement with reflectance spectrophotometry showed ischemia associated with congesti on after retransfusion. Treatment with a monoclonal antibody against e ndothelin (0.2 mg/100 g BW/h) prevented these hemodynamic disturbances , rendering a significant decrease in the total area of erosions at 20 and 60 min after retransfusion. These results strongly suggest an imp ortant role of circulating endothelin in the pathogenesis of hemorrhag ic shock-induced gastric mucosal injury through mucosal microcirculato ry perturbation.