Ablation of B- and B-kinin receptors causes cardiac dysfunction through redox-nitroso unbalance.

Aims: B- and B-kinin receptors play a major role in several cardiovascular diseases. Therefore, we aimed to evaluate cardiac functional consequences of B- and B-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- (B) and B-kinin (B) knockout mice.

Key Findings: Impaired contractility in B and B hearts was associated with oxidative stress through upregulation of NADPH oxidase p22 subunit. B and B hearts presented higher NO and peroxynitrite levels than WT. Despite decreased sarcoplasmic reticulum Ca ATPase pump (SERCA2) expression, nitration at tyrosine residues of SERCA2 was markedly higher in B and B hearts.

Significance: B- and B-kinin receptors govern ROS generation, while disruption of B- and B-kinin receptors leads to impaired cardiac dysfunction through excessive tyrosine nitration on the SERCA2 structure.