Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin
Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin
复制标题
衰老相关的胰岛素抵抗易患高血压，运动可逆转高血压：血管舒张对胰岛素的作用
DOI：
10.1007/s00395-008-0754-8
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发表时间：
2009-05-01
影响因子：
9.5
通讯作者：
Zhang, Quan-Jiang
中科院分区：
文献类型：
--
作者：
Li, Qiu-Xia;Xiong, Zheng-Ying;Zhang, Quan-Jiang
增龄是高血压的独立危险因素，高血压和胰岛素抵抗在老年人中普遍并存。本研究旨在研究年龄相关的胰岛素抵抗对血压（BP）的影响及其潜在机制，特别关注运动在逆转高血压反应中的作用。成年（6月龄）和老龄（24月龄）雄性Sprague-Dawley大鼠进行10周无负荷游泳训练（60分钟/天，5天/周）。测定动脉血管舒张、心脏收缩、eNOS激活、iNOS和gp 91 phox表达。在与年龄相关的胰岛素抵抗状态下，胰岛素输注显著升高血压（P< 0.05）。衰老导致显著的内皮功能障碍（P< 0.05 − 0.01），这是胰岛素降低动脉血管舒张的原因。增龄可减弱心肌对胰岛素的收缩反应，降低eNOS的表达和胰岛素对eNOS的磷酸化作用，增加iNOS和gp 91 phox的表达（P< 0.01）。运动改善胰岛素敏感性，增强胰岛素的正性肌力作用，促进动脉血管舒张胰岛素，增加动脉eNOS激活在成年和老龄大鼠，从而减弱胰岛素抵抗相关的高血压反应胰岛素。此外，运动显着逆转增加iNOS和gp 91 phox表达在老化的动脉。用Cavtratin或L-NAME抑制eNOS可显著阻断运动促进的动脉血管对胰岛素的舒张作用和运动降低的血压对胰岛素的反应。总之，这些结果表明，内皮功能障碍，胰岛素的反应，但不是胰岛素的正性肌力作用，在老年相关性高血压的发展中起着重要的作用。通过运动逆转高血压对胰岛素的反应很可能与eNOS依赖性方式的胰岛素敏感性改善以及氧化应激和硝化应激减少有关。
Aging is an independent risk factor for hypertension, and hypertension and insulin resistance commonly coexist in the elderly. This study was designed to examine the effects of aging-related insulin resistance on blood pressure (BP) and its underlying mechanisms, with specific focus on the role of exercise in reversing hypertensive response. Adult (6-month-old) and aging (24-month-old) male Sprague-Dawley rats were subjected to a 10 weeks free-of-loading swim training (60 min/day, 5 days/week). Arterial vasorelaxation, cardiac contraction, eNOS activation, and iNOS and gp91phoxexpression were determined. Under aging-related insulin resistance conditions, insulin infusion significantly elevated BP (P< 0.05). Aging caused significant endothelial dysfunction (P< 0.05 − 0.01), which was responsible for decreased arterial vasorelaxation to insulin. Aging attenuated myocardial contractile response to insulin, decreased eNOS expression and its phosphorylation by insulin, and increased iNOS and gp91phoxexpression in aging arteries (P< 0.01). Exercise improved insulin sensitivity, potentiated insulin’s positive inotropic effects, facilitated arterial vasorelaxation to insulin, increased arterial eNOS activation in adult and aging rats, and thus attenuated insulin resistance-related hypertensive response to insulin. Moreover, exercise markedly reversed increased iNOS and gp91phoxexpression in aging arteries. Inhibition of eNOS with Cavtratin or L-NAME significantly blocked exercise-facilitated arterial vasorelaxation to insulin and exercise-lowered BP response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin, but not insulin’s positive inotropic effects, plays an important role in the development of aging-related hypertension. The reversal of hypertensive response to insulin by exercise is most likely associated with improved insulin sensitivity in an eNOS-dependent manner and reduced oxidative and nitrative stresses.