title: Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischaemia-reperfusion injury.
abstract: 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.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.affiliation: Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.|Anesthesia and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.identifier: 0000-0003-4675-1099
authors.initials: M
authors.lastname: Hultström
authors.affiliation: Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Patzak
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Wilcox
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China. laienyin@zju.edu.cn.
authors.forename: E Y
authors.initials: EY
authors.lastname: Lai
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D002374:Catalase / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D009638:Norepinephrine
keywords: afferent arteriole; angiotensin II; catalase; hydrogen peroxide; ischaemia-reperfusion injury