Inhibition of endothelial-derived nitric oxide promotes P-selectin expression and actions in the rat microcirculation

Gastroenterology
K L DavenpeckA M Lefer

Abstract

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. 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. 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 express...Continue Reading

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