糖尿病和血糖升高对大鼠肛门尾骨肌中一氧化氮介导的神经传递的影响。

Effect of diabetes and elevated glucose on nitric oxide-mediated neurotransmission in rat anococcygeus muscle.

作者信息

Way K J, Reid J J

机构信息

Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Br J Pharmacol. 1995 Jun;115(3):409-14. doi: 10.1111/j.1476-5381.1995.tb16348.x.

DOI:10.1111/j.1476-5381.1995.tb16348.x

PMID:7582450

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908417/

Abstract

Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus muscle from 8-week streptozotocin-induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been investigated on NO-mediated relaxations, in muscles from untreated rats. 2. Relaxant responses to field stimulation (0.5-5 Hz, 10s train), sodium nitroprusside (SNP; 5 and 10 nM) and NO (1 and 3 microM) were significantly impaired in anococcygeus muscles from 8-week diabetic rats, compared to responses from control rats. Insulin treatment (5 u Lente day-1, s.c.) of diabetic rats prevented the development of this impairment. 3. Consistent with findings in 8-week diabetic rats, relaxation induced by field stimulation, SNP and NO were attenuated in tissues from 2-week and 4-week diabetic rats compared to corresponding control responses, whereas relaxations to papaverine (3 and 10 microM) were not reduced. In contrast, diabetes of 3-days duration did not affect relaxations to field stimulation, SNP or NO. 4. Incubation of anococcygeus muscles from untreated rats in medium containing elevated glucose (44.1 mM) for 6 h, significantly impaired relaxations to field stimulation compared to responses obtained after normal glucose (11.1 mM) incubation. Relaxations to SNP and to NO were not affected by 6 h exposure to elevated glucose. Similarly, incubation in hyperosmolar solutions containing mannose or sucrose for 6 h, impaired relaxations to field stimulation, but not to SNP or NO. 5. The results indicate that the diabetes-induced impairment of NO-mediated neurotransmission in the rat anococcygeus muscle develops between 3 days and 2 weeks after the induction of diabetes with streptozotocin. Prevention of the impairment by insulin treatment suggests that it is specific for the diabetic state. In addition, the impairment may be related to hyperglycaemia and the consequent rise in osmolarity, since in vitro exposure to high glucose as well as to other hyperosmolar media impaired NO-mediated relaxations to field stimulation.

摘要

一氧化氮（NO）介导的神经传递在链脲佐菌素诱导的8周龄糖尿病大鼠的肛尾肌中受损。本研究调查了胰岛素治疗以及糖尿病病程对这种损伤的影响。此外，还研究了体外暴露于高糖环境对未治疗大鼠肌肉中NO介导的舒张反应的影响。2. 与对照大鼠相比，8周龄糖尿病大鼠的肛尾肌对场刺激（0.5 - 5Hz，10s串刺激）、硝普钠（SNP；5和10nM）和NO（1和3μM）的舒张反应明显受损。糖尿病大鼠接受胰岛素治疗（5u Lente皮下注射，每日1次）可防止这种损伤的发生。3. 与8周龄糖尿病大鼠的研究结果一致，与相应的对照反应相比，2周龄和4周龄糖尿病大鼠组织中由场刺激、SNP和NO诱导的舒张反应减弱，而对罂粟碱（3和10μM）的舒张反应未降低。相反，病程为3天的糖尿病对场刺激、SNP或NO的舒张反应没有影响。4. 将未治疗大鼠的肛尾肌在含高糖（44.1mM）的培养基中孵育6小时，与在正常葡萄糖（11.1mM）孵育后获得的反应相比，对场刺激的舒张反应明显受损。暴露于高糖6小时对SNP和NO的舒张反应没有影响。同样，在含甘露糖或蔗糖的高渗溶液中孵育6小时，会损害对场刺激的舒张反应，但对SNP或NO的舒张反应没有影响。5. 结果表明，链脲佐菌素诱导糖尿病后3天至2周内，大鼠肛尾肌中糖尿病诱导的NO介导的神经传递损伤逐渐发展。胰岛素治疗可预防这种损伤，表明它是糖尿病状态所特有的。此外，这种损伤可能与高血糖及随之而来的渗透压升高有关，因为体外暴露于高糖以及其他高渗介质会损害NO介导的对场刺激的舒张反应。