Beta3‐Adrenergic Receptor Activation Alleviates Cardiac Dysfunction in Cardiac Hypertrophy by Regulating Oxidative Stress

Abstract

Background. Excessive myocardial oxidative stress could lead to the congestive heart failure. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. β3-Adrenergic receptor (AR) could regulate cardiac dysfunction proved by recent researches. The molecular mechanism of β3-AR regulating oxidative stress, especially NADPH oxidase, remains to be determined. Methods. Cardiac hypertrophy was constructed by the transverse aortic constriction (TAC) model. ROS and NADPH oxidase subunits expression were assessed after β3-AR agonist (BRL) or inhibitor (SR) administration in cardiac hypertrophy. Moreover, the cardiac function, fibrosis, heart size, oxidative stress, and cardiomyocytes apoptosis were also detected. Results. β3-AR activation significantly alleviated cardiac hypertrophy and remodeling in pressure-overloaded mice. β3-AR stimulation also improved heart function and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis. Meanwhile, β3-AR stimulation inhibited superoxide anion production and decreased NADPH oxidase activity. Furthermore, BRL treatment increased the neuronal NOS (nNOS) expression in cardiac hypertrophy. Conclusion. β3-AR stimulation alleviated cardiac dysfunction and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis by inhibiting NADPH oxidases. In addition, the protective effect of β3-AR is largely attributed to nNOS activation in cardiac hypertrophy.

Mechanical stress concealed force enhancement and ionic transient membrane potential and metabolism in akinesia of stress cardiomyopathy

“…The population with diabetes mellitus has a low risk of Takotsubo syndrome, based on myocardium-associated neuropathy preventing the emergence of ventricular ballooning [90] . However, in diabetes patients, even if the heart geometry and function are normal, impaired high-energy myocardial phosphate metabolism and a decreased mean cardiac PCr/ATP ratio are notable [91] . This could be drawn from the study of the mechanism of those who suffered from sudden Takotsubo cardiomyopathy, which was very similar to the impaired myocardium metabolic patterns are reported in Takotsubo cardiomyopathy patients [39] .…”