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

被引：47

作者：

Li, Qiu-Xia ^{[1
,2
,3
]}

Xiong, Zheng-Ying ^{[1
]}

Hu, Bai-Ping ^{[1
]}

Tian, Zhen-Jun ^{[1
]}

Zhang, Hai-Feng ^{[2
,3
]}

Gou, Wen-Yi ^{[2
,3
]}

Wang, Hai-Chang ^{[2
,3
]}

Gao, Feng ^{[2
,3
]}

Zhang, Quan-Jiang ^{[1
,2
,3
]}

机构：

[1] Shaanxi Normal Univ, Inst Phys Educ, Xian 710062, Peoples R China

[2] Fourth Mil Med Univ, Dept Physiol, Xijing Hosp, Xian 710032, Peoples R China

[3] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China

来源：

BASIC RESEARCH IN CARDIOLOGY | 2009年 / 104卷 / 03期

基金：

中国国家自然科学基金;

关键词：

hypertension; insulin resistance; endothelial dysfunction; exercise; BLOOD-PRESSURE; NITRIC-OXIDE; CARDIOVASCULAR-DISEASE; GLUCOSE-METABOLISM; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; OXIDATIVE STRESS; AEROBIC EXERCISE; RISK-FACTORS; SENSITIVITY;

D O I：

10.1007/s00395-008-0754-8

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 gp91(phox) 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 gp91(phox) 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 gp91(phox) 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.

引用

页码：269 / 284

页数：16

共 47 条

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HYPERINSULINEMIA PRODUCES BOTH SYMPATHETIC NEURAL ACTIVATION AND VASODILATION IN NORMAL HUMANS [J].