GASTRIC AND COLONIC INFLAMMATORY AND VASOACTIVE MEDIATORS IN EXPERIMENTAL PORTAL-HYPERTENSION

Rats with portal hypertension and experimental liver disease may exhib it 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 ge neration of vasoactive substances, because they may contribute to the altered mucosal function. Rats with partial vein ligation (n=7), compl ete bile duct ligation (n=6) and sham-operated rats (n=10) were studie d, 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, l eukotriene B-4, leukotriene C-4 and endothelin-1 by radioimmunoassay ( ng/g) and platelet activating factor activity (pg/10 mg) by platelet a ggregation. Pulp pressure was >13 mmHg in partial vein ligated rats an d bile duct ligated rats and 6 mmHg in sham-operated rats. No macrosco pic or microscopic lesions were seen any of the removed tissues. Gastr ic mucosal prostaglandin E(2) and thromboxane B-2 generation were decr eased by 35% and 7%, respectively, in bile duct ligated rats (bile duc t ligated versus sham-operated, p<0.05 for prostaglandin E(2) and thro mboxane B-2) Gastric leukotriene B-4 and C-4 generation, platelet acti vating factor activity and endothelin-1 content did not differ signifi cantly among the three groups. A different pattern of changes was obse rved in the colon. Colonic leukotriene Bq generation and endothelin-1 content were increased in bile duct ligated rats by 105% and 210%, res pectively (bile duct ligated versus sham-operated, p<0.05 for leukotri ene B-4 and endothelin-1). The decreased gastric mucosal prostaglandin E(2) generation of bile duct ligated rats may render the gut mucosa o f these animals relatively ischemic and vulnerable to damage by noxiou s agents. The increased colonic leukotriene Bq generation and the incr eased endothelin-1 content of the colonic mucosa of bile duct ligated rats may promote inflammatory and ischemic changes in the colonic muco sa and may enable bacterial translocation.