title: Inhibition of endothelial-derived nitric oxide promotes P-selectin expression and actions in the rat microcirculation.
abstract: OBJECTIVE
  Inhibition of nitric oxide synthesis increases leukocyte and endothelial interaction in mesenteric venules. In this study, the relationship between inhibition of NO and expression of the adhesion molecule P-selectin was examined.
  
  
  METHODS
  The rat mesentery was superfused with the NO inhibitor NG-nitro-L-arginine methyl ester (L-NAME) either alone or in combination with intravenous infusions of L-arginine, D-arginine, a P-selectin-neutralizing monoclonal antibody (PB1.3 [1 mg/kg]), recombinant human superoxide dismutase (hSOD), or 8 bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP). Leukocyte rolling and adherence were monitored in mesenteric venules via intravital microscopy. Ileal tissue superfused with L-NAME was examined immunohistochemically for P-selectin expression.
  
  
  RESULTS
  Superfusion of the rat mesentery with L-NAME resulted in a significant increase in leukocyte rolling and adherence in the mesenteric venule, which was attenuated by administration of L-arginine but not D-arginine. Monoclonal antibody PB1.3 as well as hSOD and 8-br-cGMP administered before initiation of L-NAME superfusion significantly attenuated the increase in leukocyte rolling and adherence. Immunohistochemistry showed a significant increase in P-selectin expression after 60 minutes of superfusion with L-NAME, which was attenuated by L-arginine, hSOD, and 8-br-cGMP.
  
  
  CONCLUSIONS
  These data indicate an important functional relationship between endothelial-derived NO production and expression of the endothelial adhesion molecule P-selectin.
authors.affiliation: Department of Physiology, Jefferson Medical College, Philadelphia, Pennsylvania.
authors.forename: K L
authors.initials: KL
authors.lastname: Davenpeck
authors.forename: T W
authors.initials: TW
authors.lastname: Gauthier
authors.forename: A M
authors.initials: AM
authors.lastname: Lefer
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D007082:Ileum / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation
chemical_list: D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester