Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Auton Neurosci. 2011 Jul 5;162(1-2):24-31. doi: 10.1016/j.autneu.2011.01.008. Epub 2011 Feb 21.
Cardiac autonomic neuropathy is a frequent complication of diabetes and often presents as impaired cholinergic regulation of heart rate. Some have assumed that diabetics have degeneration of cardiac cholinergic nerves, but basic knowledge on this topic is lacking. Accordingly, our goal was to evaluate the structure and function of cardiac cholinergic neurons and nerves in C57BL/6 mice with streptozotocin-induced diabetes. Electrocardiograms were obtained weekly from conscious control and diabetic mice for 16 weeks. Resting heart rate decreased in diabetic mice, but intrinsic heart rate was unchanged. Power spectral analysis of electrocardiograms revealed decreased high frequency and increased low frequency power in diabetic mice, suggesting a relative reduction of parasympathetic tone. Negative chronotropic responses to right vagal nerve stimulation were blunted in 16-week diabetic mice, but postjunctional sensitivity of isolated atria to muscarinic agonists was unchanged. Immunohistochemical analysis of hearts from diabetic and control mice showed no difference in abundance of cholinergic neurons, but cholinergic nerve density was increased at the sinoatrial node of diabetic mice (16 weeks: 14.9±1.2% area for diabetics versus 8.9±0.8% area for control, P<0.01). We conclude that disruption of cholinergic function in diabetic mice cannot be attributed to a loss of cardiac cholinergic neurons and nerve fibers or altered cholinergic sensitivity of the atria. Instead, decreased responses to vagal stimulation might be caused by a defect of preganglionic cholinergic neurons and/or ganglionic neurotransmission. The increased density of cholinergic nerves observed at the sinoatrial node of diabetic mice might be a compensatory response.
心脏自主神经病变是糖尿病的常见并发症，常表现为心率的胆碱能调节受损。有人认为糖尿病患者存在心脏胆碱能神经退行性变，但这方面的基本知识却很缺乏。因此，我们的目标是评估链脲佐菌素诱导糖尿病 C57BL/6 小鼠心脏胆碱能神经元和神经的结构和功能。每周从清醒的对照和糖尿病小鼠中获得心电图，持续 16 周。糖尿病小鼠的静息心率降低，但固有心率不变。心电图的功率谱分析显示糖尿病小鼠高频功率降低，低频功率增加，提示副交感神经张力相对降低。16 周糖尿病小鼠右侧迷走神经刺激的负性变时反应减弱，但分离心房对毒蕈碱激动剂的突触后敏感性不变。糖尿病和对照小鼠心脏的免疫组织化学分析显示，胆碱能神经元的丰度没有差异，但糖尿病小鼠窦房结的胆碱能神经密度增加（16 周：糖尿病小鼠为 14.9±1.2%，对照组为 8.9±0.8%，P<0.01）。我们的结论是，糖尿病小鼠胆碱能功能的破坏不能归因于心脏胆碱能神经元和神经纤维的丧失，或心房胆碱能敏感性的改变。相反，迷走神经刺激反应的降低可能是节前胆碱能神经元和/或神经节传递的缺陷所致。糖尿病小鼠窦房结观察到的胆碱能神经密度增加可能是一种代偿反应。
