title: Nitric oxide modulates epithelial permeability in the feline small intestine.
abstract: The objective of this study was to assess whether inhibition of nitric oxide production leads to increased epithelial permeability in feline small intestine. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine-methyl ester (L-NAME; 0.025 mumol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 90 min. An exogenous source of nitric oxide, sodium nitroprusside (SNP) was infused (0.025 mumol.ml-1.min-1) for the last 30 min of the 90-min L-NAME infusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA throughout the experiment. An increase of approximately sixfold in mucosal permeability was observed within 30 min of L-NAME infusion and this effect was completely reversed by infusion of either SNP or L-arginine (0.125 mumol.ml-1.min-1). NG-nitro-D-arginine-methyl ester (D-NAME) had no effect on mucosal permeability. The increase in epithelial permeability was sufficiently large that rhodamine-dextran (mol wt = 17,200) clearance from interstitium to lumen was increased. Pretreatment with IB4, a monoclonal antibody directed against the leukocyte adhesive glycoprotein complex (CD11/CD18) did not prevent the L-NAME-induced increase in epithelial permeability. These data suggest that inhibition of nitric oxide production leads to a reversible circulating leukocyte-independent increase in epithelial permeability.
authors.affiliation: Department of Medical Physiology, University of Calgary, Alberta, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002415:Cats; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007536:Isomerism; D009130:Muscle, Smooth / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester