Objectives: Nitric oxide (NO) is a diffusible intracellular messenger that is present in saliva. Chronic treatment with isoproterenol, a beta receptor agonist, stimulates the release of NO from acinar cells and induces salivary gland hypertrophy. The aim of this study was to investigate the effect of NO synthesis inhibitors and isoproterenol on rat salivary glands. We analyzed salivary gland weight and the number of ducts per unit area (0.5mm(2)) by NADPH-diaphorase histochemistry (to identify the presence of the enzyme NO synthase-NOS) and haematoxylin-and-eosin (HE).
Methods: For 8 days male Wistar rats received daily single intraperitoneal injections of saline or a NOS inhibitor (40mg/kg N(omega)-nitro-L-arginine L-NOARG or N(omega)-nitro-l-arginine methyl ester L-NAME). This was followed, 30min later, by subcutaneous injection of isoproterenol (2 or 5mg/kg) or saline.
Results: Isoproterenol increased parotid and submandibular gland weights. Isoproterenol (2mg/kg) induced a decrease of ducts per unit area inversely correlated to the weight of the parotid gland. This effect was augmented by L-NAME. In the submandibular gland L-NAME attenuated isoproterenol (2mg/kg) weight increase. In the submandibular gland isoproterenol and NOS inhibitors induced an increase in ducts per unit area (HE and NADPH-diaphorase). No effect was observed in the sublingual gland.
Conclusion: To our knowledge this is the first description of isoproterenol and NOS inhibitors increasing duct density in the submandibular gland. Our results corroborate the hypothesis that NO plays different roles in parotid and submandibular glands.