Niacin Prevents Leukocyte‐Endothelium Interaction Induced by eNOS Inhibition

Niacin is a lipid‐lowering agent that has been recently shown to increase eNOS expression in vitro . eNOS exerts antiinflammatory actions in the vascular system, in part via inhibition of leukocyte‐endothelium interactions (LEI). We hypothesized that niacin inhibits LEI in vivo , independently of lipid modifying effects. LEI were measured by intravital microscopy in mesenteric post‐capillary venules of live C57BL/6 mice. Endothelial dysfunction was induced by a 14‐day administration of 50 mg/kg/day of the eNOS inhibitor L‐NAME in the drinking water. Mice received three oral administrations of 50‐mg/kg niacin at 48, 24, and 2 hrs before IVM. Mice given L‐NAME exhibited increased number of rolling and adherent leukocytes (58±7.1 vs. 31±6.5 cells/min and 6±2.1 vs 2.7±0.9 cells/100 μm, respectively; p<0.01). Niacin significantly attenuated L‐NAME‐induced leukocyte rolling to 34±10 cells/min and adherence to 3.4±1.5cells/100‐μm (NS vs. control). No significant changes were observed in body weights, white blood cell counts, and plasma glucose and lipids levels in all groups of mice. Thus, niacin is an effective inhibitor of leukocyte‐endothelium interaction, independently of its metabolic action on lipids.