renalase deficiency in heart failure model of rats—a potential mechanism underlying circulating norepinephrine accumulationrenalase缺乏心力衰竭模型老鼠的潜在机制循环去甲肾上腺素积累.pdfVIP

Renalase Deficiency in Heart Failure Model of Rats—A Potential Mechanism Underlying Circulating Norepinephrine Accumulation Rong Gu, Wen Lu, Jun Xie, Jian Bai, Biao Xu* Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China Abstract Background: Sympathetic overactivity and catecholamine accumulation are important characteristic findings in heart failure, which contribute to its pathophysiology. Here, we identify a potential mechanism underlying norepinephrine accumulation in a rat model of heart failure. Methodology/Principal Findings: Initially, we constructed a rat model of unilateral renal artery stenosis (n = 16) and found that the expression of renalase, a previously identified secreted amine oxidase, was markedly reduced in the ischemic compared to the non-ischemic kidney (protein: 0.295 60.085 versus 0.76560.171, p ,0.05). Subsequently, we utilized an isolated perfused rat kidney model to demonstrate that the clearance rate of norepinephrine decreased with reduction of perfusion flow. On the basis of these findings, we hypothesized the reduced renal blood supply which occurs in heart failure would result in impaired synthesis of renalase by the kidney and consequently reduced degradation of circulating norepinephrine. To verify this, we used a rat model of infarction-induced heart failure (n = 12 per group). In these rats, the flow velocity of renal artery, when measured at four weeks, is obviously lower in the operation group. Renal expression of renalase was reduced (protein: 0.47660.043 for control, 0.24860.029 for operation versus 0.636 60.151 for sham-operation) and this was associated with an increase in circulating norepinephrine (0.168 60.016 ng/mL for control, 0.20360.019 ng/mL for operation versus 0.138 60.008