Effects of diabetes on non-adrenergic, non-cholinergic relaxation induced by GABA and electrical stimulation in the rat isolated duodenum

1. The effects of streptozotocin (STZ)-induced experimental diabetes on nit rergic-mediated responses to GABA and electrical field stimulation (EFS) ha ve been evaluated in rat isolated duodenum. 2. In the presence of noradrenergic and cholinergic blockade, EFS (60 V, 1 ms, 0.1-32 Hz) induced frequency dependent relaxations of the preparation. GABA also caused submaximal relaxation of the rat duodenum, The relaxations induced by GABA and EFS were reduced in duodenal tissues from diabetic rat s compared with control rats. 3. Neither STP- nor sodium nitroprusside-induced relaxations were altered i n diabetic duodenal tissues. GABA- and EFS-induced relaxations were inhibit ed by N-G-nitro-L-arginine methyl ester (L-NAME; 300 mmol/L) in both diabet ic and control rats. Although the inhibition caused by L-NAME of GABA- and EFS-induced relaxation was partially reversed by L-arginine (1 mmol/L), L-a rginine alone had no effect on GABA- and EFS-induced relaxation in diabetic rats. 4. These results suggest that STZ-induced diabetes impairs non-adrenergic, non-cholinergic relaxation induced by EFS and GABA. Impairment of nitrergic innervation of the rat duodenum may contribute to the abnormalities of int estinal motility abnormalities associated with diabetes.