Diabetes-Induced NOS Alteration In The Rabbit Parotid Secretion

Method: DM was induced by a single iv injection of alloxan (100 mg/kg) in rabbits.  After six weeks of diabetes duration, carbachol-induced parotid secretion was  measured before and after administration of inhibitors of NOS in control and  diabetic rabbits.

Results: Carbachol-induced parotid secretion was halved  in diabetic rabbits. In the presence of N(G) -nitro-l-arginine (L-NOARG), a non-selective inhibitor of NOS,  and L-N(omega)-nitroarginine-2,4-L-diaminobutyric-amide (N^w), a selective inhibitor of neuronal NOS, maximal carbachol-induced parotid secretion was reduced in control (997.0±84.0 vs 498.5±45.5 and  997.0±84.0 vs 650.0±39.8, respectively) and diabetic (485.5±32.5 vs 160.0±28.7 and 485.5±32.5 vs 315.0±25.5, respectively) rabbits.  S-methylisothiourea (SMT), a selective inhibitor of inducible NOS (iNOS), decreased secretion only in diabetic rabbits. Comparison of differences of area under the dose-response curves (dAUC) values showed that inhibitory effects of L-NOARG and SMT were increased and of N^w unchanged under DM.

Conclusion: In DM, increased function of NOS, due to an increase of iNOS function, was associated with the decreased cholinergically-induced rabbit parotid secretion.