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Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin

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Abstract

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 gp91phox expression 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 gp91phox expression 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 gp91phox expression 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.

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Acknowledgments

This study was supported by National Science Fund for Outstanding Young Investigators (No. 30625033), grants from the National Natural Science Foundation of China (Nos. 30500577; 30800397), and National Basic Research Program of China (973 Program, No. 2007CB512106).

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Authors and Affiliations

  1. Institution of Physical Education, Shaanxi Normal University, Xi’an, 710062, China

    Qiu-Xia Li, Zheng-Ying Xiong, Bai-Ping Hu, Zhen-Jun Tian MD, PhD & Quan-Jiang Zhang MD, PhD

  2. Depts. of Physiology and Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

    Qiu-Xia Li, Hai-Feng Zhang, Wen-Yi Gou, Hai-Chang Wang, Feng Gao & Quan-Jiang Zhang MD, PhD

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  1. Qiu-Xia Li
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Correspondence to Quan-Jiang Zhang MD, PhD.

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Returned for 1. Revision: 18 February 2008 1. Revision received: 11 August 2008

Returned for 2. Revision: 10 September 2008 2. Revision received: 15 September 2008

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Li, QX., Xiong, ZY., Hu, BP. et al. Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin. Basic Res Cardiol 104, 269–284 (2009). https://doi.org/10.1007/s00395-008-0754-8

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