Title
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Ablation of B₁- and B₂-kinin receptors causes cardiac dysfunction through redox-nitroso unbalance
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Author
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Abstract
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Aims: B-1- and B-2-kinin receptors play a major role in several cardiovascular diseases. Therefore, we aimed to evaluate cardiac functional consequences of B-1- and B-2-kinin receptors ablation, focusing on the cardiac ROS and NO generation. Main methods: Cardiac contractility, ROS, and NO generation, and protein expression were evaluated in male wild-type (WT), B-1- (B-1(-/-)) and B-2-kinin (B-2(-/-)) knockout mice. Key findings: Impaired contractility in B-1(-/-) and B-2(-/-) hearts was associated with oxidative stress through upregulation of NADPH oxidase p22(phox) subunit. B(1)(-/- )and B-2(-/-) hearts presented higher NO and peroxynitrite levels than WT. Despite decreased sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2) expression, nitration at tyrosine residues of SERCA2 was markedly higher in B-1(-/- ) and B(2)(-/- )hearts. Significance: B-1- and B-2-kinin receptors govern ROS generation, while disruption of B-1- and B-2-kinin receptors leads to impaired cardiac dysfunction through excessive tyrosine nitration on the SERCA2 structure. |
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Language
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English
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Source (journal)
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Life sciences. - Oxford, 1973, currens
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Publication
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Oxford
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2019
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ISSN
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0024-3205
[print]
1879-0631
[online]
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DOI
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10.1016/J.LFS.2019.04.062
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Volume/pages
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228
(2019)
, p. 121-127
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ISI
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000468185400013
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Pubmed ID
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31039364
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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