Role of proinflammatory cytokines and redox homeostasis in exercise-induced delayed progression of hypertension in spontaneously hypertensive rats.

Role of proinflammatory cytokines and redox homeostasis in exercise-induced delayed progression of hypertension in spontaneously hypertensive rats.
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DOI:
10.1161/hypertensionaha.109.135459
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发表时间:
2009-12
期刊:
Hypertension (Dallas, Tex. : 1979)
影响因子:
--
通讯作者:
Francis J
Francis J
中科院分区:
其他
文献类型:
--
作者:
Agarwal D;Haque M;Sriramula S;Mariappan N;Pariaut R;Francis J

文献摘要

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高血压是各种心血管疾病的众所周知的危险因素。最近,运动已被推荐为所有高血压患者生活方式改变的一部分。然而,运动训练(ExT)诱导的高血压发展的确切机制知之甚少。因此,我们假设,慢性ExT将延迟年轻自发性高血压大鼠(SHR)的高血压的进展。此外,我们探讨了慢性ExT的有益作用是否是通过减少促炎细胞因子(PIC)和改善氧化还原状态介导的。我们还研究了NF-κB在运动诱导效应中的参与。为了验证我们的假设,年轻的血压正常(WKY)和自发性高血压大鼠(SHR)给予中等强度的ExT 16周。血压测定采用尾袖法,心功能评价采用超声心动图。采用电子顺磁共振光谱法测定心肌总活性氧(ROS)和超氧阴离子(O2·−)产生量;采用实时PCR法测定TNF-α、IL-1β、gp 91 phox和iNOS;采用EMSA法测定NF-κB活性。慢性ExT在高血压大鼠中导致显著降低血压,减少向心性肥厚和改善舒张功能。ExT显着降低PIC,iNOS,减弱总ROS和O2·−的产生,并增加SHR的抗氧化剂。ExT还导致SHR NO生成增加,NF-κB活性降低。总之,慢性ExT延缓了年轻SHR的高血压进展并改善了心功能;这些ExT诱导的有益作用是通过减少PIC和通过下调NF-κB改善氧化还原稳态介导的。
Hypertension is a well-known risk factor for various cardiovascular diseases. Recently, exercise has been recommended as a part of lifestyle modification for all hypertensive patients. However, the precise mechanisms of exercise training (ExT)-induced effects on the development of hypertension are poorly understood. Therefore, we hypothesized that chronic ExT would delay the progression of hypertension in young spontaneously hypertensive rats (SHR). In addition, we explored whether the beneficial effects of chronic ExT were mediated by reduced pro-inflammatory cytokines (PICs) and improved redox status. We also investigated the involvement of NF-κB in exercise-induced effects. To test our hypotheses, young normotensive (WKY) and spontaneously hypertensive rats (SHR) were given moderate-intensity ExT for 16 weeks. Blood pressure was determined by the tail-cuff method and cardiac function was assessed by echocardiography. Myocardial total reactive oxygen species (ROS) and superoxide (O2•−) production were measured by electron paramagnetic resonance spectroscopy; TNF-α, IL-1β, gp91phox and iNOS by real-time PCR, and NF-κB activity by EMSA. Chronic ExT in hypertensive rats resulted in significantly reduced blood pressure, reduced concentric hypertrophy and improved diastolic function. ExT significantly reduced PICs, iNOS, attenuated total ROS and O2•− production, and increased antioxidants in SHR. ExT also resulted in increased nitric oxide production and decreased NF-κB activity in SHR. In summary, chronic ExT delays the progression of hypertension and improves cardiac function in young SHR; these ExT-induced beneficial effects are mediated by reduced PICs and improved redox homeostasis via downregulation of NF-κB.