title: Increased gastric bicarbonate secretion in portal hypertensive anesthetized rats: role of prostaglandins and nitric oxide.
abstract: Gastric bicarbonate secretion might be modified in portal hypertension as a consequence of the intramucosal increase in prostaglandins and nitric oxide content. Therefore, we studied gastric bicarbonate secretion in control and portal hypertensive rats and investigated the role of prostaglandins and nitric oxide. Basal gastric bicarbonate secretion was studied in rats, using a gastric pH back-titration technique, two weeks after partial portal vein ligation or a sham operation. The effects of the following drugs were investigated: the prostaglandin synthase inhibitor indomethacin (5 mg/kg intravenously), prostaglandin (PGE2) (1 mg/kg intravenously), the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg intravenously) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg/kg intravenously), and the nitric oxide donor nitroprusside (5 mmol/liter in the gastric perfusate). Plasma leakage in the gastric wall was also measured after Evans blue dye injection in portal hypertensive and sham-operated rats pretreated by indomethacin (5 mg/kg, intravenously) and L-NAME (5 mg/kg, intravenously). Basal bicarbonate secretion was significantly increased in portal hypertensive rats as compared to controls. After indomethacin, the bicarbonate secretion was significantly reduced to a similar level in both groups. PGE2 increased bicarbonate secretion significantly more in portal hypertensive rats than in sham-operated rats. The NO synthase inhibitor L-NMMA significantly increased bicarbonate secretion in portal hypertensive rats only, while the other inhibitor, L-NAME, increased it significantly more in portal hypertensive than in the sham-operated rats. Plasma leakage in portal hypertensive rats, which was increased in the basal condition as compared to control, was further enhanced by indomethacin but not by L-NAME pretreatment. The nitric oxide donor significantly reduced bicarbonate secretion in portal hypertensive rats to reach a similar level as in sham-operated rats. Basal gastric bicarbonate secretion is increased in portal hypertensive rats. This could be due to an enhanced prostaglandin mucosal level. Nitric oxide, which reduces bicarbonate secretion, may contribute to limiting prostaglandin-induced bicarbonate overproduction.
authors.affiliation: Service d'Hépatologie-Gastroentérologie and INSERM U99, Hôpital Henri Mondor, Creteil, France.
authors.forename: D
authors.initials: D
authors.lastname: Lamarque
authors.forename: C
authors.initials: C
authors.lastname: Dutreuil
authors.forename: D
authors.initials: D
authors.lastname: Dhumeaux
authors.forename: J C
authors.initials: JC
authors.lastname: Delchier
mesh_terms: D000758:Anesthesia; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D017082:Portal Pressure / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000098:blood supply; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin