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Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension?

机译:肾脏的氧化应激和一氧化氮缺乏症:与高血压的关键联系?

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There is growing evidence that oxidative stress contributes to hypertension. Oxidative stress can precede the development of hypertension. In almost all models of hypertension, there is oxidative stress that, if corrected, lowers BP, whereas creation of oxidative stress in normal animals can cause hypertension. There is overexpression of the p22(phox) and Nox-1 components of NADPH oxidase and reduced expression of extracellular superoxide dismutase (EC-SOD) in the kidneys of ANG II-infused rodents, whereas there is overexpression of p47(phox) and gp91(phox) and reduced expression of intracellular SOD with salt loading. Several mechanisms have been identified that can make oxidative stress self-sustaining. Reactive oxygen species (ROS) can enhance afferent arteriolar tone and reactivity both indirectly via potentiation of tubuloglomerular feedback and directly by microvascular mechanisms that diminish endothelium-derived relaxation factoritric oxide responses, generate a cyclooxygenase-2-dependent endothelial-derived contracting factor that activates thromboxane-prostanoid receptors, and enhance vascular smooth muscle cells reactivity. ROS can diminish the efficiency with which the kidney uses O(2) for Na(+) transport and thereby diminish the P(O(2)) within the kidney cortex. This may place a break on further ROS generation yet could further enhance vasculopathy and hypertension. There is a tight relationship between oxidative stress in the kidney and the development and maintenance of hypertension.
机译:越来越多的证据表明氧化应激会导致高血压。氧化应激可先于高血压发展。在几乎所有的高血压模型中,都有氧化应激,如果纠正,会降低血压,而在正常动物中产生氧化应激会导致高血压。 NADPH氧化酶的p22(phox)和Nox-1组分过表达,并在注入ANG II的啮齿动物肾脏中降低细胞外超氧化物歧化酶(EC-SOD)的表达,而p47(phox)和gp91则过表达(phox)并降低了盐负荷下细胞内SOD的表达。已经确定了几种可以使氧化应激自我维持的机制。活性氧(ROS)可以通过增强肾小管肾反馈间接或直接通过微血管机制来增强传入小动脉的张力和反应性,这些机制会减少内皮源性舒张因子/一氧化氮反应,产生环氧化酶2依赖性内皮源性收缩因子,激活血栓烷-前列腺素受体,并增强血管平滑肌细胞反应性。 ROS可以减少肾脏使用O(2)进行Na(+)转运的效率,从而减少肾脏皮质内的P(O(2))。这可能会中断进一步的ROS生成,但可能进一步加剧血管病变和高血压。肾脏的氧化应激与高血压的发生和维持之间存在紧密的关系。

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