Local l-NAME decreases blood flow and increases leukocyte adhesion via CD18.

Local inhibition of nitric oxide (NO) synthesis withl-arginine analogs such as N G-nitro-l-arginine methyl ester (l-NAME) decreased red blood cell velocity ( V RBC) in capillaries and increased leukocyte adhesion in postcapillary venules in rat skeletal muscle. The goal of the present study was to determine the mechanism of this response tol-NAME. Using intravital videomicroscopy, we examined blood flow in the surface microvasculature of rat extensor digitorum longus muscle.l-NAME (30 mM in the pipette) locally applied to capillaries (300 μm from feeding arteriole) reduced V RBC[control V RBC = 244 ± 53 (SE) μm/s; Δ V RBC = -52 ± 8%] and increased leukocyte adhesion (from 0.2 ± 0.01 to 1.3 ± 0.3 cells/100 μm) in control animals. Systemic pretreatment with fucoidan (selectin binder), superoxide dismutase and catalase (extracellular antioxidants), dimethylthiourea (intracellular antioxidant), or ketotifen (mast cell stabilizer) did not alter this response. Pretreatment with CL26, an anti-CD18 antibody, abolished the l-NAME response. Our results suggest that l-NAME increased leukocyte-endothelial interactions via an effect on CD11/CD18 or its ligand, intercellular adhesion molecule.