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Impairment of nitrergic‐mediated relaxation of rat isolated duodenum by experimental diabetes
Author(s) -
MartinezCuesta M.A.,
Massuda H.,
Whittle B.J.R.,
Moncada S.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13291.x
Subject(s) - endocrinology , medicine , acetylcholine , duodenum , sodium nitroprusside , chemistry , streptozotocin , nitric oxide , nicotine , nitric oxide synthase , cholinergic , diabetes mellitus , biology
1 Diabetes mellitus is associated with changes in gastrointestinal motility. 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 investigated. 2 The non‐adrenergic, non‐cholinergic (NANC) relaxation of the isolated duodenum induced by nicotine (0.3 – 10 μ m ) or the nicotinic agonist, 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP; 10 μ m ) was inhibited by the NO synthase inhibitor, N G ‐nitro‐ l ‐arginine (3–100 μ m ). 3 This nitrergic relaxation induced by nicotine or DMPP of the duodenum from diabetic rats was substantially smaller than that of the tissue from control rats. 4 By contrast, the relaxation of the duodenum from diabetic rats to the NO donor, nitroprusside (0.3–10 μ m ) was similar to that of control tissue, whereas the relaxation to ATP (0.1–3 μ m ) was enhanced to a small but significant degree. 5 Incubation of duodenal tissue from control rats at 4°C for 72 h, which leads to neuronal 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‐dependent relaxation of rat aortic rings induced by acetylcholine (0.01–2 μ m ). 6 The calcium‐dependent NO synthase activity in duodenal tissue, determined by the conversion of radiolabelled l ‐arginine to citrulline, was significantly reduced in cold‐stored tissue and in tissue obtained from diabetic rats. 7 These findings in the rat duodenum indicate that a reduction in intestinal NO synthase activity is associated with an impairment of the NANC relaxation. A defect in the intestinal nitrergic innervation could thus contribute to the motility dysfunction observed in diabetes.