Local L-NAME decreases blood flow and increases leukocyte adhesion via CD18.
Local inhibition of nitric oxide (NO) synthesis with L-arginine analogs such as NG-nitro-L-arginine methyl ester (L-NAME) decreased red blood cell velocity (VRBC) 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 to L-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 microns from feeding arteriole) reduced VRBC [control VRBC = 244 +/- 53 (SE) microns/s; delta VRBC = -52 +/- 8%] and increased leukocyte adhesion (from 0.2 +/- 0.01 to 1.3 +/- 0.3 cells/100 microns) 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.
Mitchell
D J
DJ
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
Yu
J
J
Tyml
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D018821:CD18 Antigens; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester