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PLoS One. 2011 Jan 31;6(1):e14633. doi: 10.1371/journal.pone.0014633.

Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.

Author information

1
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±0.085 versus 0.765±0.171, 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: 0.476±0.043 for control, 0.248±0.029 for operation versus 0.636±0.151 for sham-operation) and this was associated with an increase in circulating norepinephrine (0.168±0.016 ng/mL for control, 0.203±0.019 ng/mL for operation versus 0.138±0.008 ng/mL for sham-operation).

CONCLUSIONS/SIGNIFICANCE:

Renalase expression is influenced by renal blood flow and impaired synthesis of renalase by the kidney may represent a potential mechanism underlying circulating norepinephrine accumulation in heart failure.

PMID:
21297953
PMCID:
PMC3031511
DOI:
10.1371/journal.pone.0014633
[Indexed for MEDLINE]
Free PMC Article

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