Nitric oxide modulates epithelial permeability in the feline small intestine.
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.
Kubes
P
P
Department of Medical Physiology, University of Calgary, Alberta, Canada.
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
D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester