INVOLVEMENT OF NITRIC-OXIDE AND PROSTAGLANDINS IN GASTRIC-MUCOSAL HYPEREMIA OF PORTAL-HYPERTENSIVE ANESTHETIZED RATS

This study investigates the effects of inhibition of nitric oxide synt hesis by N(G)-nitro-L-arginine methyl ester (L-NAME), the inhibition o f prostaglandin synthesis with indomethacin and the combined effects o n gastric mucosal hyperemia of ketamine-anesthetized rats with portal hypertension induced by partial portal vein ligation. The hydrogen gas -clearance technique was used for measurement of gastric mucosal blood flow. Blood pressure increased with L-NAME administration in a simila r manner in portal-hypertensive and sham-operated rats. Low doses of L -NAME (1 and 3 mg/kg, intravenously) caused a significant and dose-dep endent reduction in gastric mucosal blood flow in portal-hypertensive rats but had no effect on sham-operated animals. With a higher dose of L-NAME (13 mg/kg, intravenously), a significant decrease in gastric m ucosal blood flow was observed in both portal-hypertensive and sham-op erated rats. Indomethacin pretreatment (5 mg/kg, subcutaneously) cause d a significant decrease in basal gastric mucosal blood flow of portal -hypertensive rats but did not modify this parameter in sham-operated animals. In sham-operated rats pretreated with indomethacin, the lower dose of L-NAME (3 mg/kg) did not significantly modify basal gastric m ucosal blood flow. Likewise, pretreatment with indomethacin in sham-op erated rats did not augment the significant reduction in gastric mucos al blood flow produced by the higher dose of L-NAME. In portal-hyperte nsive rats the significant dose-dependent reduction in gastric mucosal blood flow induced by L-NAME (3 and 13 mg/kg) was not significantly a ltered by pretreatment with indomethacin. Portal pressure was higher i n portal-hypertensive than in sham-operated rats, and no significant d ifferences were observed in this parameter between portal-hypertensive animals treated with different doses of L-NAME. These results indicat e that both nitric oxide and prostaglandins may be involved in the gas tric mucosal hyperemia of portal-hypertensive rats. However, no synerg istic interactions between these two endogenous vasodilators could be observed in this experimental model.