Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension
Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension
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DOI：
10.1161/circulationaha.108.824730
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发表时间：
2009-02-24
期刊：
影响因子：
37.8
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
--
作者：
Nagae, Ai;Fujita, Megumi;Fujita, Toshiro
背景-肥胖是心血管疾病的主要危险因素之一，通常与氧化应激和交感神经兴奋增加有关。我们已经提出，在盐敏感性高血压中，大脑中氧化应激的增加会调节动脉压的交感神经调节，而盐敏感性高血压通常与肥胖有关。本研究旨在确定氧化应激是否可以在肥胖诱发的高血压的初始阶段介导中枢交感神经兴奋。 方法和结果-4周龄的雄性Sprague-Dawley大鼠被喂以高脂肪（45％kcal脂肪）或低脂肪（10％kcal脂肪）饮食6周。脂肪负荷会引起高血压和交感神经兴奋，以及内脏肥胖。在乌拉坦麻醉和人工通气的大鼠中，当将 53 或 105 μmol/kg tempol（一种膜渗透性超氧化物歧化酶模拟物）注入侧脑室时，动脉压和肾交感神经活动以剂量依赖性方式下降。与低脂饮食喂养的正常血压大鼠相比，中枢颞叶醇在高脂饮食喂养的高血压大鼠中显着更大程度地降低动脉压和肾交感神经活动。脑室内注射罗布麻宁或二亚苯基碘鎓（一种还原性 NADPH 氧化酶抑制剂）也能显着降低高脂饮食喂养大鼠的动脉压和肾交感神经活动。此外，脂肪负荷增加了下丘脑中 NADPH 氧化酶的活性以及 NADPH 氧化酶亚基 p22(phox)、p47(phox) 和 gp91(phox) mRNA 的表达。结论：在肥胖诱发的高血压中，大脑中氧化应激的增加（可能通过 NADPH 氧化酶的激活）可能通过中枢交感神经兴奋促进高血压的进展。 （流通。2009 年；119：978-986。）
Background-Obesity is one of the major risk factors for cardiovascular disease and is often associated with increased oxidative stress and sympathoexcitation. We have already suggested that increased oxidative stress in the brain modulates the sympathetic regulation of arterial pressure in salt-sensitive hypertension, which is often associated with obesity. The present study was performed to determine whether oxidative stress could mediate central sympathoexcitation in the initial stage of obesity-induced hypertension.Methods and Results-Four-week-old male Sprague-Dawley rats were fed a high-fat (45% kcal as fat) or low-fat (10% kcal as fat) diet for 6 weeks. Fat loading elicited hypertension and sympathoexcitation, along with visceral obesity. In urethane-anesthetized and artificially ventilated rats, arterial pressure and renal sympathetic nerve activity decreased in a dose-dependent fashion when 53 or 105 mu mol/kg tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. Central tempol reduced arterial pressure and renal sympathetic nerve activity to a significantly greater extent in high-fat diet-fed hypertensive rats than in low-fat diet-fed normotensive rats. Intracerebroventricular apocynin or diphenyleneiodonium, a reduced NADPH oxidase inhibitor, also elicited markedly greater reductions in arterial pressure and renal sympathetic nerve activity in the high-fat diet-fed rats. In addition, fat loading increased NADPH oxidase activity and NADPH oxidase subunit p22(phox), p47(phox), and gp91(phox) mRNA expression in the hypothalamus.Conclusions-In obesity-induced hypertension, increased oxidative stress in the brain, possibly via activation of NADPH oxidase, may contribute to the progression of hypertension through central sympathoexcitation. (Circulation. 2009; 119: 978-986.)