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

Abstract

Aims: B₁- and B₂-kinin receptors play a major role in several cardiovascular diseases. Therefore, we aimed to evaluate cardiac functional consequences of B₁- and B₂-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), B₁- (B₁^-/-) and B₂-kinin (B₂^-/-) knockout mice.

Key findings: Impaired contractility in B₁^-/- and B₂^-/- hearts was associated with oxidative stress through upregulation of NADPH oxidase p22^phox subunit. B₁^-/- and B₂^-/- 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 B₁^-/- and B₂^-/- hearts.

Significance: B₁- and B₂-kinin receptors govern ROS generation, while disruption of B₁- and B₂-kinin receptors leads to impaired cardiac dysfunction through excessive tyrosine nitration on the SERCA2 structure.

Keywords: Cardiac; Kinin receptors; NADPH oxidase; Nitric oxide; Reactive oxygen species.