1. Ablation of B 1 - and B 2 -kinin receptors causes cardiac dysfunction through redox-nitroso unbalance.
- Author
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Mesquita TRR, Miguel-Dos-Santos R, Jesus ICG, de Almeida GKM, Fernandes VA, Gomes AAL, Guatimosim S, Martins-Silva L, Ferreira AJ, Capettini LDSA, Pesquero JL, and Lauton-Santos S
- Subjects
- Animals, Gene Deletion, Heart Diseases physiopathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardial Contraction, NADPH Oxidases metabolism, Nitric Oxide metabolism, Oxidation-Reduction, Reactive Oxygen Species metabolism, Receptor, Bradykinin B1 metabolism, Receptor, Bradykinin B2 metabolism, Heart physiopathology, Heart Diseases genetics, Receptor, Bradykinin B1 genetics, Receptor, Bradykinin B2 genetics
- Abstract
Aims: B
1 - 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 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., 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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