Way K J, Reid J J
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Neuropharmacology. 1994 Nov;33(11):1315-22. doi: 10.1016/0028-3908(94)90031-0.
The contribution of advanced glycation end-product (AGE) formation to alterations in nitrergic neurotransmission caused by 8-week streptozotocin-induced diabetes has been examined in the rat anococcygeus muscle. Relaxant responses to nitrergic nerve stimulation (0.5-5 Hz, 10-sec train), to nitric oxide (NO; 0.1-3 microM), to the NO donor, sodium nitroprusside (SNP; 5-500 nM), and to the cell-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP (15 and 30 microM), were significantly smaller in muscles from diabetic rats than from control rats. Pretreatment with aminoguanidine hemisulphate (1 milligram drinking water) to inhibit AGE formation, did not alter the relaxant responses to nitrergic nerve stimulation, NO or SNP in tissues from control rats, or responses to NO or SNP in tissues from diabetic rats, however relaxations to nitrergic nerve stimulation were further reduced in tissues from diabetic rats. In anococcygeus muscles from untreated animals, a 20-min exposure to aminoguanidine (1 mM) in vitro had no effect on relaxations to nitrergic nerve stimulation. The results suggest that diabetes impairs nitrergic transmission in the rat anococcygeus at least partly through alterations in the cGMP-relaxation pathway. The impaired neurotransmission does not appear to be related to the formation of AGEs.
在大鼠尾骨肌中，研究了晚期糖基化终产物（AGE）形成对8周链脲佐菌素诱导的糖尿病所致氮能神经传递改变的影响。糖尿病大鼠肌肉对氮能神经刺激（0.5 - 5Hz，10秒串刺激）、一氧化氮（NO；0.1 - 3μM）、NO供体硝普钠（SNP；5 - 500nM）以及环磷酸鸟苷（cGMP）的细胞可渗透类似物8-溴-cGMP（15和30μM）的舒张反应，显著小于对照大鼠肌肉。用半硫酸氨基胍（1毫克饮用水）预处理以抑制AGE形成，对对照大鼠组织中氮能神经刺激、NO或SNP的舒张反应无影响，对糖尿病大鼠组织中NO或SNP的反应也无影响，然而糖尿病大鼠组织中对氮能神经刺激的舒张反应进一步降低。在未处理动物的尾骨肌中，体外暴露于氨基胍（1mM）20分钟对氮能神经刺激的舒张反应无影响。结果表明，糖尿病至少部分通过cGMP舒张途径的改变损害大鼠尾骨肌中的氮能传递。神经传递受损似乎与AGEs的形成无关。
