This study investigates the effects of inhibition of nitric oxide synthesis by NG‐nitro‐L‐arginine methyl ester (L‐NAME), the inhibition of prostaglandin synthesis with indomethacin and the combined ...effects on 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 similar manner in portal‐hypertensive and sham‐operated rats. Low doses of L‐NAME (1 and 3 mg/kg, intravenously) caused a significant and dosedependent reduction in gastric mucosal blood flow in portal‐hypertensive rats but had no effect on shamoperated animals. With a higher dose of L‐NAME (13 mg/kg, intravenously), a significant decrease in gastric mucosal blood flow was observed in both portal‐hypertensive and sham‐operated rats. Indomethacin pretreatment (5 mg/kg, subcutaneously) caused 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 mucosal blood flow. Likewise, pretreatment with indomethacin in sham‐operated rats did not augment the significant reduction in gastric mucosal blood flow produced by the higher dose of L‐NAME. In portal‐hypertensive rats the significant dose‐dependent reduction in gastric mucosal blood flow induced by L‐NAME (3 and 13 mg/kg) was not significantly altered by pretreatment with indomethacin. Portal pressure was higher in portal‐hypertensive than in sham‐operated rats, and no significant differences were observed in this parameter between portal‐hypertensive animals treated with different doses of L‐NAME. These results indicate that both nitric oxide and prostaglandins may be involved in the gastric mucosal hyperemia of portal‐hypertensive rats. However, no synergistic interactions between these two endogenous vasodilators could be observed in this experimental model. (HEPATOLOGY 1993;18:628–634.)
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