Calorie Restriction Prevents Hypertension and Cardiac Hypertrophy in the Spontaneously Hypertensive Rat
Calorie Restriction Prevents Hypertension and Cardiac Hypertrophy in the Spontaneously Hypertensive Rat
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DOI：
10.1161/hypertensionaha.110.154732
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发表时间：
2010-09-01
期刊：
影响因子：
8.3
通讯作者：
Dyck, Jason R. B.
中科院分区：
文献类型：
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作者：
Dolinsky, Vernon W.;Morton, Jude S.;Dyck, Jason R. B.
由于最近的证据表明，卡路里限制(CR)具有许多有益的心血管效应，我们研究了短期CR是否可以降低非肥胖自发性高血压大鼠(SHR)的高血压和防止固有的心肌肥厚。在自由喂养或短期CR的5周后，接受短期CR的SHR分别通过无创性尾袖血压测量和超声心动图评估收缩压(BP)降低和左室壁厚度减少。此外，股动脉的超声测量显示，与对照组相比，CR组SHR的血流介导的血管扩张显著改善。此外，离体肠系膜动脉的压力肌图和随后的组织学和生化分析表明，与即刻喂养的SHR相比，短期CR改善了血管顺应性，增加了内皮型一氧化氮合酶(ENOS)的活性和一氧化氮的生物利用度，并减少了血管重构。尽管这些影响可能是多因素的，但它们与循环脂肪因子、脂联素水平升高和AMP激活蛋白激酶(AMPK)活性增强有关。为了证明SHR中脂联素水平的升高足以防止血压升高，腺病毒介导的脂联素过表达增加了循环中的脂联素水平，降低了血压，并在没有CR的情况下激活了AMPK/eNOS通路。总体而言，我们的发现提供了令人信服的证据，表明短期CR通过刺激脂联素/AMPK/eNOS信号轴在SHR中发挥有益作用。因此，CR可能是一种有效的非药物治疗高血压，靶向脂联素/AMPK/eNOS通路可能会改善高血压的治疗。(高血压。2010；56：412-421。)
Because recent evidence demonstrated that calorie restriction (CR) has numerous beneficial cardiovascular effects, we investigated whether short-term CR could reduce hypertension and prevent cardiac hypertrophy inherent to the nonobese spontaneously hypertensive rat (SHR). After 5 weeks of either ad libitum feeding or short-term CR, SHRs subjected to short-term CR had lower systolic blood pressure (BP) and reduced left ventricular wall thickness as assessed by noninvasive tail-cuff BP measurements and echocardiography, respectively. In addition, ultrasound measurements of the femoral artery revealed that flow-mediated vasodilation was significantly improved in SHRs with CR compared to controls. Moreover, pressure myography of isolated mesenteric arteries and subsequent histological and biochemical analysis of these arteries demonstrated that short-term CR improved vascular compliance, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide bioavailability, and reduced vascular remodeling compared to ad libitum-fed SHRs. Although these effects are likely multifactorial, they were associated with elevated levels of the circulating adipokine, adiponectin, and enhanced AMP-activated protein kinase (AMPK) activity. To provide evidence that elevated adiponectin levels in the SHR is sufficient to prevent an increase in BP, adenoviral-mediated overexpression of adiponectin increased circulating levels of adiponectin, reduced BP, and activated the AMPK/eNOS pathway in the absence of CR. Overall, our findings provide compelling evidence that short-term CR exerts beneficial effects in the SHR via stimulation of an adiponectin/AMPK/eNOS signaling axis. As a result, CR may serve as an effective nonpharmacological treatment of hypertension, and targeting the adiponectin/AMPK/eNOS pathway may improve treatment of hypertension. (Hypertension. 2010;56:412-421.)