LOCAL L-NAME DECREASES BLOOD-FLOW AND INCREASES LEUKOCYTE ADHESION VIA CD18

Local inhibition of nitric oxide (NO) synthesis with L-arginine analog s such as N-G-nitro-L-arginine methyl ester (L-NAME) decreased red blo od cell velocity (V-RBC) in capillaries and increased leukocyte adhesi on in postcapillary venules in rat skeletal muscle. The goal of the pr esent study was to determine the mechanism of this response to L-NAME. Using intravital videomicroscopy, we examined blood flow in the surfa ce microvasculature of rat extensor digitorum longus muscle. L-NAME (3 0 mM in the pipette) locally applied to capillaries (300 mu m from fee ding arteriole) reduced V-RBC [control V-RBC = 244 +/- 53 (SE) mu m/s; Delta V-RBC = -52 +/- 8%] and increased leukocyte adhesion (from 0.2 +/- 0.01 to 1.3 +/- 0.3 cells/100 mu m) in control animals. Systemic p retreatment with fucoidan (selectin binder), super-oxide dismutase and catalase (extracellular antioxidants), dimethylthiourea (intracellula r antioxidant), or ketotifen (mast cell stabilizer) did not alter this response. Pretreatment with CL26, an anti-CD18 antibody, abolished th e L-NAME response. Our results suggest that L-NAME increased leukocyte -endothelial interactions via an effect on CD11/CD18 or its ligand, in tercellular adhesion molecule.