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Increased hydrogen peroxide impairs angiotensin II contractions of afferent arterioles in mice after renal ischaemia–reperfusion injury
Author(s) -
Huang Q.,
Wang Q.,
Zhang S.,
Jiang S.,
Zhao L.,
Yu L.,
Hultström M.,
Patzak A.,
Li L.,
Wilcox C. S.,
Lai E. Y.
Publication year - 2016
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12745
Subject(s) - afferent arterioles , endocrinology , medicine , catalase , angiotensin ii , chemistry , renal cortex , reactive oxygen species , superoxide , contraction (grammar) , kidney , receptor , oxidative stress , biochemistry , enzyme
Abstract Aim 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 ( O 2 − ) or hydrogen peroxide (H 2 O 2 ). Methods Renal afferent arterioles were isolated and perfused from C57 BL /6 mice 24 h after IRI or sham surgery. Responses to Ang II or noradrenaline were assessed by measuring arteriolar diameter. Production of H 2 O 2 and O 2 − 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. Results 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 H 2 O 2 ( P < 0.001) and a 45% decrease in catalase activity ( P < 0.01). Contractions were reduced in normal arterioles after incubation with H 2 O 2 (−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 AT 1 R expression. Conclusions Renal IRI in mice selectively impairs afferent arteriolar responses to Ang II because of H 2 O 2 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.