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.