ROLE OF NITRIC-OXIDE IN SJOGRENS-SYNDROME

Objective. To measure levels of salivary nitrite (NO2-) and to localiz e nitric oxide synthases (NOS) in the labial salivary glands (LSGs) of patients with Sjogren's syndrome (SS). Methods. NO2- was measured by the Griess reaction, LSGs were analyzed using NADPH-diaphorase histoch emical and immunohistochemical studies to determine the constitutive N OS (neuronal [ncNOS] and endothelial [ecNOS]) and inducible NOS (iNOS) isoforms. Results. The NO2- concentration (mean+/-SEM 307+/-51 mu M v ersus 97+/-16 mu M; P <0.05) and output (166+/-46 nmoles/minute versus 37+/-7 nmoles/minute) were increased in SS patients compared with hea lthy control subjects, NADPH-diaphorase was found in some nerve fibers and endothelial cells, and, in SS, was found in myoepithelial, acinar , and ductal epithelial cells, but in only a few inflammatory cells, I n SS, ncNOS-immunoreactive nerve fibers were sparse and ecNOS was foun d in a minority of the CD31-positive vascular endothelial cells and ac inar cells, whereas iNOS was localized in myoepithelial, acinar, and d uctal epithelial cells, often together with tumor necrosis factor alph a. Conclusion. Nitrite was found in normal human saliva, NO produced b y ncNOS probably acts as a nonadrenergic, noncholinergic neurotransmit ter, whereas that produced by ecNOS exerts a vasodilatory effect. SS p atients had increased NO2- concentrations, with most of the superfluou s salivary NO being produced not by the immigrant inflammatory cells, but rather, by the resident salivary gland cells, NO may contribute to inflammatory damage and acinar cell atrophy in SS.