Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease
Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease
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DOI：
10.1161/hypertensionaha.111.182923
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发表时间：
2012-01-01
期刊：
影响因子：
8.3
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
--
作者：
Fujita, Megumi;Ando, Katsuyuki;Fujita, Toshiro
高血压在慢性肾脏疾病中非常普遍，对其预后至关重要。交感神经兴奋和氧化应激已被证明参与慢性肾脏疾病。我们以前已经表明，脑氧化应激介导的交感神经兴奋盐敏感性高血压模型，达尔盐敏感大鼠动脉压升高。因此，我们研究了过度脑氧化应激引起的交感神经兴奋是否会导致盐诱导的慢性肾病模型大鼠动脉压升高。将年轻（3周龄）雄性Sprague-Dawley大鼠随机分配至单侧肾切除术或假手术组，然后给予正常盐（0.5%）或高盐（8.0%）饮食4周。年轻的盐负荷单侧肾切除大鼠表现出交感神经兴奋，高血压，肾损伤，蛋白尿和全球肾小球硬化连同肾小管间质损害。尿烷麻醉和人工通气下，肾交感神经活动，动脉压，心率下降到更大程度的盐加载uninephrectomized大鼠比non-salt-loaded uninephrectomized大鼠和盐加载或non-salt-loaded假手术大鼠，当Tempol，膜渗透性超氧化物歧化酶模拟物，急性注入侧脑室。光泽精化学发光法测定的下丘脑的氧化应激也显著增加。此外，在盐负荷单侧肾切除大鼠中，慢性脑室内Tempol抗氧化剂治疗降低了交感神经活动和动脉压，这反过来又导致肾损伤减少。通过口服中枢交感神经阻滞剂莫索尼定治疗引起了类似的效应。总之，脑氧化应激引起的交感神经兴奋可能介导盐诱导的慢性肾脏疾病的动脉压升高。（高血压。2012; 59：105 - 112.）。在线补充资料
Hypertension is very prevalent in chronic kidney disease and critical for its prognosis. Sympathoexcitation and oxidative stress have been demonstrated to be involved in chronic kidney disease. We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in the salt-sensitive hypertension model, Dahl salt-sensitive rats. Thus, we investigated whether sympathoexcitation by excessive brain oxidative stress could contribute to arterial pressure elevation in salt-induced chronic kidney disease model rats. Young (3-week-old) male Sprague-Dawley rats were randomly assigned to a uninephrectomy or sham operation and then subjected to either a normal salt (0.5%) or high-salt (8.0%) diet for 4 weeks. The young salt-loaded uninephrectomized rats exhibited sympathoexcitation, hypertension, and renal injury, proteinuria and global glomerulosclerosis together with tubulointerstitial damage. Under urethane anesthesia and artificial ventilation, renal sympathetic nerve activity, arterial pressure, and heart rate decreased to a greater degree in the salt-loaded uninephrectomized rats than in the nonsalt-loaded uninephrectomized rats and the salt-loaded or nonsalt-loaded sham-operated rats, when Tempol, a membrane-permeable superoxide dismutase mimetic, was infused acutely into the lateral cerebral ventricle. Oxidative stress in the hypothalamus, measured by lucigenin chemiluminescence, was also significantly greater. Furthermore, in the salt-loaded uninephrectomized rats, antioxidant treatment with chronic intracerebroventricular Tempol decreased sympathetic nerve activity and arterial pressure, which, in turn, led to a decrease in renal damage. Similar effects were elicited by treatment with oral moxonidine, the central sympatholytic agent. In conclusion, sympathoexcitation by brain oxidative stress may mediate arterial pressure elevation in salt-induced chronic kidney disease. (Hypertension. 2012;59:105-112.). Online Data Supplement