Gastric and colonic inflammatory and vasoactive mediators in experimental portal hypertension

Rats with portal hypertension and experimental liver disease may exhibit increased susceptibility of the gastric mucosa to damage by noxious agents, and increased bacterial translocation through the bowel wall. The aim of this study was to determine mucosal gastric and colonic generation of vasoactive substances, because they may contribute to the altered mucosal function. Rats with partial vein ligation (n=7), complete bile duct ligation (n=6) and sham-operated rats (n=10) were studied. Three weeks following surgery rats were anesthetized, splenic pulp pressure was measured, stomachs and colons were removed and mucosa was extracted for determination of prostaglandin E 2 , thromboxane B 2 , leukotriene B 4 , leukotriene C 4 and endothelin-l by radioimmunoassay (ng/g) and platelet activating factor activity (pg/10 mg) by platelet aggregation. Pulp pressure was >13 mmHg in partial vein ligated rats and bile duct ligated rats and 6 mmHg in sham-operated rats. No macroscopic or microscopic lesions were seen any of the removed tissues. Gastric mucosal prostaglandin E 2 and thromboxane B 2 generation were decreased by 35% and 7%, respectively, in bile duct ligated rats (bile duct ligated versus sham-operated, p<0.05 for prostaglandin E 2 and thromboxane B 2 ). Gastric leukotriene B 4 and C 4 generation, platelet activating factor activity and endothelin-l content did not differ significantly among the three groups. A different pattern of changes was observed in the colon. Colonic leukotriene B 4 generation and endothelin-l content were increased in bile duct ligated rats by 105% and 210%, respectively (bile duct ligated versus sham-operated, p<0.05 for leukotriene B 4 and endothelin-l). The decreased gastric mucosal prostaglandin E 2 generation of bile duct ligated rats may render the gut mucosa of these animals relatively ischemic and vulnerable to damage by noxious agents. The increased colonic leukotriene B 4 generation and the increased endothelin-1 content of the colonic mucosa of bile duct ligated rats may promote inflammatory and ischemic changes in the colonic mucosa and may enable bacterial translocation.