Effects of NO synthase inhibitors on the synovial microcirculation in the mouse knee joint

Production of nitric oxide by the inducible NO synthase (iNOS) is known to be enhanced in chronic joint inflammation and osteoarthritis as well as ase ptic loosening of joint prostheses. Initial studies yielded promising resul ts 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 de veloped model for the in vivo study of synovial microcirculation in the mou se knee joint, the effects of selective versus nonselective inhibition of i NOS 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 densit y (FCD), diameter of venules, venular red blood cell velocity and leukocyte -endothelial cell interaction were quantitatively analyzed before, and 10 a nd 60 min after intravenous injection of NOS inhibitors [selective iNOS inh ibitor N-iminoethyl-L-lysine (L-NIL), and nonselective NOS inhibitor N-G-ni tro-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-en dothelial cell interaction in the synovium, indicating its potential use fo r selective inhibition of iNOS in joint inflammation. Using our method, fur ther studies will provide new insights into the unknown effect of NOS inhib ition on the synovial microvasculature in inflammatory joint disease in viv o. Copyright (C) 1999 S. Karger AG, Basel.