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

Author

Thássio Ricardo Ribeiro Mesquita

Affiliation

Department of Physiology, Federal University of Sergipe, Sergipe, Brazil; Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, United States of America. Electronic address: [Email]

Abstract

OBJECTIVE : 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.
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.
RESULTS : Impaired contractility in B1-/- and B2-/- hearts was associated with oxidative stress through upregulation of NADPH oxidase p22phox 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.
CONCLUSIONS : 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,