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      Effects of NO Synthase Inhibitors on the Synovial Microcirculation in the Mouse Knee Joint


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          Production of nitric oxide by the inducible NO synthase (iNOS) is known to be enhanced in chronic joint inflammation and osteoarthritis as well as aseptic loosening of joint prostheses. Initial studies yielded promising results after inhibition of the nitric oxide synthase (NOS). However, the effect of NOS inhibition has not been studied at the site of the primary function of NO, the microcirculation of the synovium in vivo. Using our recently developed model for the in vivo study of synovial microcirculation in the mouse knee joint, the effects of selective versus nonselective inhibition of iNOS were investigated by means of intravital fluorescence microscopy. After resection of the patella tendon, the synovial fatty tissue was exposed for intravital microscopy. Diameter of arterioles, functional capillary density (FCD), diameter of venules, venular red blood cell velocity and leukocyte-endothelial cell interaction were quantitatively analyzed before, and 10 and 60 min after intravenous injection of NOS inhibitors [selective iNOS inhibitor N-iminoethyl- L-lysine (L-NIL), and nonselective NOS inhibitor N<sup>G</sup>-nitro- L-arginine methyl ester (L-NAME)]. Our results demonstrate that L-NAME causes a significant decrease in the arteriolar diameter and FCD associated with an increase in the leukocyte accumulation in the synovium in vivo. In contrast, L-NIL neither altered the microhemodynamics nor the leukocyte-endothelial cell interaction in the synovium, indicating its potential use for selective inhibition of iNOS in joint inflammation. Using our method, further studies will provide new insights into the unknown effect of NOS inhibition on the synovial microvasculature in inflammatory joint disease in vivo.

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          Suppression of arthritis by an inhibitor of nitric oxide synthase

          Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.
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            Inhibition of Endothelial Vascular Cell Adhesion Molecule-1 Expression by Nitric Oxide Involves the Induction and Nuclear Translocation of IκBα


              Author and article information

              J Vasc Res
              Journal of Vascular Research
              S. Karger AG
              October 1999
              28 October 1999
              : 36
              : 5
              : 379-384
              aDepartment of Orthopedics and bInstitute for Surgical Research, Ludwig Maximilians University of Munich, Germany
              25677 J Vasc Res 1999;36:379–384
              © 1999 S. Karger AG, Basel

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              Page count
              Figures: 3, Tables: 1, References: 27, Pages: 6
              Research Paper

              General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
              Knee joint,Synovial microcirculation,Mouse,Arthritis,L-NAME,L-NIL,Nitric oxide


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