Hydrogen peroxide impairs angiotensin Ⅱ contraction of afferent arteriole in mice with renal ischemia-reperfusion injury

Renal ischemia reperfusion injury increases renal generation of angiotensin II （Ang Ⅱ） which could wors- en renal vasocontraction. Thus, we investigated the hypothesis that renal ischemia reperfusion injury alters renal af- ferent arteriolar responses to Ang II via production of hydrogen peroxide （ H202 ）, or superoxide （ O2 ） or via al- tered angiotensin type 1 receptor （AT1R） expression. Afferent arterioles of mouse kidneys 24h after renal ischemia repeffusion or sham procedures were isolated and perfused. Responses to Ang II or norepinephrine （NE） were as- sessed by measurement of arteriolar luminal diameter. The mRNA expressions of AT1 receptor （ AT1 R） and AT2 re- ceptor （ATzR） were evaluated by quantificational real-time polymerase chain reaction. Compared to sham group, afferent arterioles from mouse kidneys after renal ischemia reperfusion had impaired contractions to Ang II （ -4.63 ± 3.06） % versus （ - 29.95 ± 1.31 ） % at 10 -9 tool · ^-1, p 〈 0.05 , （ - 27.07 ± 1 50） % versus （ - 41 74 ± 0.60） % at 10^-7 tool · L^-1, P 〈 0.05 ） that were normalized by incubation with PEG-catalase , but unaffected by PEG-SOD. However, the NE responses of afferent arterioles after renal ischemia reperfusion were unchanged. Com- pared to the sham group, renal ischemia reperfusion significantly increased the renal cortical H202 （0. 123 ± -1 0. 006） versus （0. 087 ± 0. 003） mmol·mg protein, P 〈 0.01 ）, reduced catalase activity [ （ 14.81 ± 3.22） ver- sus （28.49 ± 1.62） units · mg^-1 protein, P 〈 0.01 ] and downregulated mRNA for AT1R （0.27 ± 0.02 versus 0.95 ± 0.02, P 〈 0.01 ）. We conclude that afferent arteriolar responses to Ang II are impaired selectively in mice after renal ischemia reperfusion by accumulation of H202 and reduced expression of AT1R.