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

<h4>Background</h4>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.<h...

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Autores principales: Rong Gu, Wen Lu, Jun Xie, Jian Bai, Biao Xu
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:adad94df698740c9a91e90f90e03d3e02021-11-18T06:59:33ZRenalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.1932-620310.1371/journal.pone.0014633https://doaj.org/article/adad94df698740c9a91e90f90e03d3e02011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21297953/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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).<h4>Conclusions/significance</h4>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.Rong GuWen LuJun XieJian BaiBiao XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14633 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rong Gu
Wen Lu
Jun Xie
Jian Bai
Biao Xu
Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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).<h4>Conclusions/significance</h4>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.
format article
author Rong Gu
Wen Lu
Jun Xie
Jian Bai
Biao Xu
author_facet Rong Gu
Wen Lu
Jun Xie
Jian Bai
Biao Xu
author_sort Rong Gu
title Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
title_short Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
title_full Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
title_fullStr Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
title_full_unstemmed Renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
title_sort renalase deficiency in heart failure model of rats--a potential mechanism underlying circulating norepinephrine accumulation.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/adad94df698740c9a91e90f90e03d3e0
work_keys_str_mv AT ronggu renalasedeficiencyinheartfailuremodelofratsapotentialmechanismunderlyingcirculatingnorepinephrineaccumulation
AT wenlu renalasedeficiencyinheartfailuremodelofratsapotentialmechanismunderlyingcirculatingnorepinephrineaccumulation
AT junxie renalasedeficiencyinheartfailuremodelofratsapotentialmechanismunderlyingcirculatingnorepinephrineaccumulation
AT jianbai renalasedeficiencyinheartfailuremodelofratsapotentialmechanismunderlyingcirculatingnorepinephrineaccumulation
AT biaoxu renalasedeficiencyinheartfailuremodelofratsapotentialmechanismunderlyingcirculatingnorepinephrineaccumulation
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