IMPAIRMENT OF NITRERGIC-MEDIATED RELAXATION OF RAT ISOLATED DUODENUM BY EXPERIMENTAL DIABETES

1 Diabetes mellitus is associated with changes in gastrointestinal mot ility. The effects of experimental diabetes, induced by streptozotocin administration to rats 3-4 weeks previously, on the nitric oxide (NO) -mediated (nitrergic) relaxation of the duodenum have now been investi gated. 2 The non-adrenergic, non-cholinergic (NANC) relaxation of the isolated duodenum induced by nicotine (0.3-10 mu M) or the nicotinic a gonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP; 10 mu M) was inhibite d by the NO synthase inhibitor, N-G-nitro-L-arginine (3-100 mu M). 3 T his nitrergic relaxation induced by nicotine or DMPP of the duodenum f rom diabetic rats was substantially smaller than that of the tissue fr om control rats. 4 By contrast, the relaxation of the duodenum from di abetic rats to the NO donor, nitroprusside (0.3-10 mu M) was similar t o that of control tissue, whereas the relaxation to ATP (0.1-3 mu M) w as enhanced to a small but significant degree. 5 Incubation of duodena l tissue from control rats at 4 degrees C for 72 h, which leads to neu ronal disruption, significantly attenuated the relaxation to nicotine or DMPP whereas the relaxation induced by nitroprusside or ATP was not affected. Comparable cold-storage did not affect the endothelium-depe ndent relaxation of rat aortic rings induced by acetylcholine (0.01-2 mu M). 6 The calcium-dependent NO synthase activity in duodenal tissue , determined by the conversion of radiolabelled L-arginine to citrulli ne, was significantly reduced in cold-stored tissue and in tissue obta ined from diabetic rats. 7 These findings in the rat duodenum indicate that a reduction in intestinal NO synthase activity is associated wit h an impairment of the NANC relaxation. A defect in the intestinal nit rergic innervation could thus contribute to the motility dysfunction o bserved in diabetes.