Ablation of B₁- and B₂-kinin receptors causes cardiac dysfunction through redox-nitroso unbalance

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.

Language

English

Source (journal)

Life sciences. - Oxford, 1973, currens

Publication

Oxford : 2019

ISSN

0024-3205 [print]

1879-0631 [online]

DOI

10.1016/J.LFS.2019.04.062

Volume/pages