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 hemorrhagic 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 were induced with this experimental protocol. The total area of erosions was minimal only at the end of hypotension, and increased time-dependently after blood retransfusion. Plasma endothelin concentration significantly increased at the end of hypotension and persistently increased after retransfusion, whereas in gastric endothelin concentration a significant increase was observed at 60 min after retransfusion. The gastric mucosal hemodynamics as assessed by continuous measurement with reflectance spectrophotometry showed ischemia associated with congestion after retransfusion. Treatment with a monoclonal antibody against endothelin (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 important role of circulating endothelin in the pathogenesis of hemorrhagic shock-induced gastric mucosal injury through mucosal microcirculatory perturbation.