Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischaemia-reperfusion injury.
Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischaemia-reperfusion injury.
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DOI：
10.1111/apha.12745
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Lai EY
中科院分区：
文献类型：
--
作者：
Huang Q;Wang Q;Zhang S;Jiang S;Zhao L;Yu L;Hultström M;Patzak A;Li L;Wilcox CS;Lai EY
肾缺血再灌注损伤(IRI)增加血管紧张素II(Ang II)和活性氧(ROS)，这是强大的血管功能调节剂。然而，单个ROS的作用及其与Ang II的相互作用尚不清楚。在这里，我们验证了这样的假设，即IRI通过增加超氧阴离子(O2，․−)或过氧化氢(H_2O_2)来调节肾传入小动脉对血管紧张素Ⅱ的反应。分别于IRI或假手术后24小时分离和灌流C57BL/6小鼠的肾传入小动脉。通过测量小动脉直径来评估血管紧张素II或去甲肾上腺素的反应。在传入小动脉和肾皮质检测H_2O_2和O_2-․−的产生。检测肾小球前小动脉和肾皮质超氧化物歧化酶、过氧化氢酶活性及血管紧张素Ⅱ受体基因表达。再灌注后小鼠的传入小动脉对血管紧张素Ⅱ的最大收缩减少(−27±2%对−42±1%，P<；0.001)，但对去甲肾上腺素保持正常收缩。缺血再灌注后的小动脉过氧化氢含量增加38%(P<；0.001)，过氧化氢酶活性降低45%(P<；0.01)。正常小动脉经H_2O_2孵育后收缩减少(−为22±2%，−为42±1%，P<；0.05)，与IRI相似。然而，尽管AT1R的表达减少，但通过与聚乙二醇过氧化氢酶孵育，受损的收缩可以恢复正常。小鼠肾脏IRI选择性地损害对Ang II的传入小动脉反应，因为过氧化氢酶活性降低引起的过氧化氢积聚。这可能是一种保护机制，对血管紧张素转换酶II的作用有一定的缓冲作用。
Renal ischemia reperfusion injury (IRI) increases angiotensin II (Ang II) and reactive oxygen species (ROS) that are potent modulators of vascular function. However, the roles of individual ROS and their interaction with Ang II are not clear. Here we tested the hypothesis that IRI modulates renal afferent arteriolar responses to Ang II via increasing superoxide (O2․−) or hydrogen peroxide (H2O2). Renal afferent arterioles were isolated and perfused from C57BL/6 mice 24 hours after IRI or sham surgery. Responses to Ang II or norepinephrine were assessed by measuring arteriolar diameter. Production of H2O2 and O2․− were assessed in afferent arterioles and renal cortex. Activity of SOD and catalase, and mRNA expressions of Ang II receptors were assessed in pre-glomerular arterioles and renal cortex. Afferent arterioles from mice after IRI had a reduced maximal contraction to Ang II (−27±2% versus −42±1%, P<0.001), but retained a normal contraction to norepinephrine. Arterioles after IRI had a 38% increase in H2O2 (P<0.001) and a 45% decrease in catalase activity (P<0.01). Contractions were reduced in normal arterioles after incubation with H2O2 (−22±2% versus −42±1%, P<0.05) similar to the effects of IRI. However, the impaired contractions were normalized by incubation with PEG-catalase despite a reduced AT1R expression. Renal IRI in mice selectively impairs afferent arteriolar responses to Ang II because of H2O2 accumulation that is caused by a reduced catalase activity. This could serve to buffer the effect of Ang II after IRI, and may be a protective mechanism.
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DOI：
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发表时间：
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期刊：
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Hypertension (Dallas, Tex. : 1979)
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