MODULATION OF OXIDIZED LOW-DENSITY LIPOPROTEIN-INDUCED MICROVASCULAR DYSFUNCTION BY NITRIC-OXIDE

The objectives of this study were to determine 1) whether the leukocyte-endothelial cell adhesion in postcapillary venules elicited by copper-oxidized low-density lipoproteins (Cu-LDL) is accompanied by enhanced vascular albumin leakage and mast cell degranulation and 2) whether nitric oxide (NO) donors attenuate the Cu-LDL-induced microvascular dysfunction. Infusion of Cu-LDL, but not normal LDL, caused significant increases in leukocyte rolling, adherence, emigration, mast cell degranulation, and an enhanced albumin leakage in rat mesenteric venules. Treatment with the NO donors sodium nitroprusside and spermine-NO or pretreatment with superoxide dismutase or L-arginine significantly reduced the Cu-LDL-induced leukocyte adherence, emigration, mast cell degranulation, and albumin leakage, whereas spermine and D-arginine had no effect. These results indicate that NO protects the microvasculature against the deleterious effects of oxidized LDL, an effect that may be related to NO's ability to reduce leukocyte-endothelial cell adhesion and/or prevent mast cell degranulation.