title: Role of eNOS-derived NO in the postischemic anti-inflammatory effects of antecedent ethanol ingestion in murine small intestine.
abstract: Ingestion of low levels of ethanol 24 h before [ethanol preconditioning (EPC)] ischemia and reperfusion (I/R) prevents postischemic leukocyte rolling (LR) and adhesion (LA), effects that were abolished by adenosine A(2) receptor (ADO-A(2)R) antagonists or nitric oxide (NO) synthase (NOS) inhibitors. The aims of this study were to determine whether NO derived from endothelial NOS (eNOS) during the period of ethanol exposure triggered entrance into this preconditioned state and whether these events were initiated by an ADO-A(2)R-dependent mechanism. Ethanol or distilled water vehicle was administered to C57BL/6J [wild type (WT)] or eNOS-deficient (eNOS-/-) mice by gavage. Twenty-four hours later, the superior mesenteric artery was occluded for 45 min. LR and LA were quantified by intravital microscopy after 30 and 60 min of reperfusion. I/R increased LR and LA in WT mice, effects that were abolished by EPC or NO donor preconditioning (NO-PC). NO-PC was not attenuated by coincident administration of an ADO-A(2)R antagonist. I/R increased LR and LA in eNOS-/- mice to levels comparable with those noted in WT animals. However, EPC only slightly attenuated postischemic LR and LA, whereas NO-PC remained effective as a preconditioning stimulus in eNOS-/- mice. Preconditioning with an ADO-A(2)R agonist (which we previously demonstrated prevents I/R-induced LR and LA in WT animals) failed to attenuate these postischemic adhesive responses in eNOS-/- mice. Our results indicate that EPC is triggered by NO formed secondary to ADO-A(2)R-dependent eNOS activation during the period of ethanol exposure 24 h before I/R.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, School of Medicine, Shreveport, LA, USA.
authors.forename: Taiji
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kamada
authors.forename: Catherine
authors.initials: C
authors.lastname: Dayton
authors.forename: F Spencer
authors.initials: FS
authors.lastname: Gaskin
authors.forename: Mozow
authors.initials: M
authors.lastname: Yusof
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Patsy
authors.initials: P
authors.lastname: Carter
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Korthuis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000378:metabolism*; D015424:Reperfusion
chemical_list: D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D000431:Ethanol; D052250:Nitric Oxide Synthase Type III