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

Abstract 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 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.