Hicks K K, Seifen E, Stimers J R, Kennedy R H
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
J Auton Nerv Syst. 1998 Mar 3;69(1):21-30. doi: 10.1016/s0165-1838(98)00004-6.
Diabetes-associated alterations in resting heart rate and blood pressure have been demonstrated in clinical studies and in animal models of insulin-dependent diabetes mellitus (IDDM). These alterations may result from changes in the heart, vasculature or autonomic nervous system control. Using the streptozotocin- (STZ-) treated rat model of IDDM, the current study was designed to: (1) monitor changes in heart rate and blood pressure continually during a 10-week period in conscious unrestrained animals; and (2) determine if observed alterations in heart rate were mediated by changes in sympathetic and/or parasympathetic nervous control. Biotelemetry techniques were used. Heart rate and blood pressure were recorded 24 h a day at 10 min intervals before and after induction of diabetes. Diabetes was induced by i.v. administration of 50 mg/kg STZ. Resting autonomic nervous system tone was estimated by chronotropic responses to full-blocking doses of nadolol (5 mg/kg i.p.) and atropine (10 mg/kg i.p.). STZ-induced diabetes was associated with time-dependent reductions in heart rate and its circadian variation. Diastolic blood pressure and mean arterial pressure did not differ significantly when compared between control and STZ-treated animals; however, pulse pressure was diminished in diabetic rats. Chronotropic responses to both nadolol and atropine were blunted significantly in diabetic animals suggesting that resting levels of both vagal and sympathetic nervous tone to the heart were diminished. Heart rate in the presence of both nadolol and atropine was also decreased in diabetic rats. All effects observed following administration of STZ were reversed, at least in part, by insulin treatment. These results suggest that IDDM is associated with time-dependent reductions in resting heart rate and autonomic nervous control of cardiac function.
临床研究及胰岛素依赖型糖尿病(IDDM)动物模型均已证实,糖尿病与静息心率及血压的改变有关。这些改变可能源于心脏、血管系统或自主神经系统控制的变化。本研究采用链脲佐菌素(STZ)处理的IDDM大鼠模型,旨在:(1)在10周内持续监测清醒无束缚动物的心率和血压变化;(2)确定观察到的心率改变是否由交感神经和/或副交感神经控制的变化介导。采用生物遥测技术。在诱导糖尿病前后,每隔10分钟记录一次心率和血压,每天记录24小时。通过静脉注射50mg/kg STZ诱导糖尿病。通过对纳多洛尔(5mg/kg腹腔注射)和阿托品(10mg/kg腹腔注射)的完全阻断剂量的变时反应来估计静息自主神经系统张力。STZ诱导的糖尿病与心率及其昼夜变化的时间依赖性降低有关。与对照组和STZ处理组动物相比,舒张压和平均动脉压无显著差异;然而,糖尿病大鼠的脉压减小。糖尿病动物对纳多洛尔和阿托品的变时反应均明显减弱,提示心脏迷走神经和交感神经的静息张力均降低。糖尿病大鼠在同时使用纳多洛尔和阿托品时心率也降低。给予STZ后观察到的所有效应至少部分被胰岛素治疗逆转。这些结果表明,IDDM与静息心率的时间依赖性降低以及心脏功能的自主神经控制有关。