Mediators of Leukocyte Adhesion in Rat Mesenteric Venules Elicited by Inhibition of Nitric Oxide Synthesis

Background: Inhibitors of nitric oxide production promote leukocyte adherence and emigration in postcapillary venules. The objective of this study was to determine if the enhanced leukocyte adherence and emigration associated with inhibition of NO production involves inflammatory agents such as platelet-activating factor (PAF) and leukotriene B4 (LTB4) and/or phospholipase A2 (PLA2).

Methods: The rat mesentery was superfused with the inhibitor of NO production NG-nitro-L-arginine methyl ester (L-NAME) either alone or in combination with WEB2086 (PAF receptor antagonist), SC41930 (LTB4 receptor antagonist), or quinacrine (PLA2 inhibitor). The number of adherent and emigrated leukocytes, leukocyte rolling velocity, erythrocyte velocity, venular blood flow, and shear rate were monitored in mesenteric venules.

Results: L-NAME alone induced a dramatic increase in leukocyte adherence (10-fold) and emigration (4-fold). Treatment with SC41930 significantly reduced, whereas either WEB2086 or quinacrine completely abolished, the increased leukocyte adherence and emigration induced by L-NAME.

Conclusions: These observations suggest that the increased leukocyte adherence and emigration associated with inhibition of NO synthesis involves PLA2 activation and is mediated by PAF and LTB4.