Hong Ling-Zong, Hsieh Po-Shiuan
Department of Education and Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Am J Hypertens. 2007 Apr;20(4):451-8. doi: 10.1016/j.amjhyper.2006.11.004.
The present study was undertaken to compare the effects of chronic hyperinsulinemia with or without insulin resistance on the autonomic control of heart rate (HR) in rats.
Male Sprague-Dawley rats were implanted subcutaneously with insulin (3 mU/kg x min) or vehicle-filled osmotic minipumps for 8 weeks. Insulin-infused rats were further divided into insulin resistant (IR) and insulin sensitive (IS) groups according to the results of the homeostasis model assessment method and euglycemic hyperinsulinemic clamp study. Autonomic function in HR control was indicated by arterial baroreflex sensitivity (BRS) after a bolus injection of phenylephrine or sodium nitroprusside.
Compared with those in control group, plasma insulin levels were elevated about threefold and 1.5-fold in the IR and IS groups at the end of week 8, respectively. Blood glucose level remained basal in the IR group, but was significantly lower in the IS group. The elevated mean arterial pressure (MAP) observed in IR was not exhibited in IS. The HR and BRS in reflex tachycardia were significantly increased in the IR and IS groups, but the BRS in reflex bradycardia was not different among all rats. Propranolol eliminated the tachycardia and enhanced BRS responses in both groups. Methylatropine further accelerated tachycardia and diminished the enhanced BRS in the IR group. However, in IS, the enhanced BRS remained after methylatropine was given. The intrinsic HR was similar among all groups. The baseline MAP, HR, and BRS in reflex tachycardia were significantly correlated to plasma insulin levels but not to the Si value, an index of insulin sensitivity.
The present results demonstrate that hyperinsulinemia but not insulin resistance is a dominant contributing factor to the development of arterial baroreflex abnormalities in this chronic hyperinsulinemic model, which may simultaneously enhance sympathetic nerve activity and possibly vagal withdrawal if insulin resistance coexisted.
本研究旨在比较慢性高胰岛素血症伴或不伴胰岛素抵抗对大鼠心率自主控制的影响。
将雄性Sprague-Dawley大鼠皮下植入胰岛素（3 mU/kg×min）或装有赋形剂的渗透微型泵，持续8周。根据稳态模型评估法和正常血糖高胰岛素钳夹研究结果，将输注胰岛素的大鼠进一步分为胰岛素抵抗（IR）组和胰岛素敏感（IS）组。通过注射去氧肾上腺素或硝普钠后动脉压力反射敏感性（BRS）来表示心率控制中的自主功能。
与对照组相比，第8周结束时，IR组和IS组的血浆胰岛素水平分别升高约3倍和1.5倍。IR组血糖水平维持在基础水平，但IS组血糖水平显著降低。IR组观察到平均动脉压（MAP）升高，而IS组未出现。IR组和IS组反射性心动过速时的心率和BRS显著增加，但所有大鼠反射性心动过缓时的BRS无差异。普萘洛尔消除了两组的心动过速并增强了BRS反应。甲基阿托品进一步加速了IR组的心动过速并减弱了增强的BRS。然而，在IS组中，给予甲基阿托品后增强的BRS仍然存在。各组的固有心率相似。反射性心动过速时的基线MAP、心率和BRS与血浆胰岛素水平显著相关，但与胰岛素敏感性指数Si值无关。
目前的结果表明，在这种慢性高胰岛素血症模型中，高胰岛素血症而非胰岛素抵抗是动脉压力反射异常发展的主要促成因素，如果同时存在胰岛素抵抗，可能会同时增强交感神经活动并可能导致迷走神经撤离。
