Ablation of B_1- and B_2-kinin receptors causes cardiac dysfunction through redox-nitroso unbalance

摘要

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 peroxyni-trite levels than WT. Despite decreased sarcoplasmic reticulum Ca~2+ 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.