Huang Q, Wang Q, Zhang S, Jiang S, Zhao L, Yu L, Hultström M, Patzak A, Li L, Wilcox C S, Lai E Y
Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
College of Life Sciences, Zhejiang University, Hangzhou, China.
Acta Physiol (Oxf). 2016 Oct;218(2):136-45. doi: 10.1111/apha.12745. Epub 2016 Jul 15.
Renal ischaemia-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 (H2 O2 ).
Renal afferent arterioles were isolated and perfused from C57BL/6 mice 24 h after IRI or sham surgery. Responses to Ang II or noradrenaline were assessed by measuring arteriolar diameter. Production of H2 O2 and O2- was 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 vs. -42±1%, P < 0.001), but retained a normal contraction to noradrenaline. Arterioles after IRI had a 38% increase in H2 O2 (P < 0.001) and a 45% decrease in catalase activity (P < 0.01). Contractions were reduced in normal arterioles after incubation with H2 O2 (-22±2 vs. -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 AT1 R expression.
Renal IRI in mice selectively impairs afferent arteriolar responses to Ang II because of H2 O2 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.
肾缺血再灌注损伤（IRI）会增加血管紧张素II（Ang II）和活性氧（ROS），它们是血管功能的强效调节剂。然而，单个ROS的作用及其与Ang II的相互作用尚不清楚。在此，我们检验了以下假设：IRI通过增加超氧化物（O2-）或过氧化氢（H2O2）来调节肾传入小动脉对Ang II的反应。
在IRI或假手术后24小时，从C57BL/6小鼠分离并灌注肾传入小动脉。通过测量小动脉直径评估对Ang II或去甲肾上腺素的反应。在传入小动脉和肾皮质中评估H2O2和O2-的产生。在肾小球前小动脉和肾皮质中评估超氧化物歧化酶（SOD）和过氧化氢酶的活性以及Ang II受体的mRNA表达。
IRI后小鼠的传入小动脉对Ang II的最大收缩反应降低（-27±2%对-42±1%，P<0.001），但对去甲肾上腺素的收缩反应保持正常。IRI后的小动脉H2O2增加38%（P<0.001），过氧化氢酶活性降低45%（P<0.01）。与IRI的作用相似，正常小动脉在与H2O2孵育后收缩反应降低（-22±2%对-42±1%，P<0.05）。然而，尽管AT1R表达降低，但通过与聚乙二醇过氧化氢酶孵育，受损的收缩反应恢复正常。
小鼠肾IRI选择性损害传入小动脉对Ang II的反应，这是由于过氧化氢酶活性降低导致H2O2积累。这可能有助于缓冲IRI后Ang II的作用，可能是一种保护机制。
