The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure

Abstract

Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits.Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6 mg kg −1 day −1 ), or placebo for 30 days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment.NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

Extracellular Vesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells Protect Against DOX-Induced Heart Failure Through the miR-100-5p/NOX4 Pathway

“…Cardiomyocyte oxidative stress plays an important role in heart failure ( Kim et al, 2020 ). In heart failure, oxidative stress is markedly increased ( Wang et al, 2019 ; Lubrano and Balzan, 2020 ). Inhibition of oxidative stress in cardiomyocytes can improve the symptoms of heart failure ( Kumar et al, 2019 ; Pop et al, 2020 ).…”

Effective Accentuation of Voltage-Gated Sodium Current Caused by Apocynin (4′-Hydroxy-3′-methoxyacetophenone), a Known NADPH-Oxidase Inhibitor

“…Of note, this compound has been widely used as a selective inhibitor of NADPH-dependent oxidase (NOX) [2][3][4][5]. Alternatively, it has been recognized to be one of the most promising drugs in a variety of pathophysiological disorders, such as inflammatory and neurodegenerative diseases, glioma, and cardiac failure [1,3,[5][6][7][8][9][10][11] aPO has been recently shown to ameliorate cardiac function (e.g., structural remodeling) in heart failure [6,7,[11][12][13]. Pituitary cells were previously demonstrated to be expressed in the activity of NOX [14,15].…”

“…Of note, this compound has been widely used as a selective inhibitor of NADPH-dependent oxidase (NOX) [ 2 , 3 , 4 , 5 ]. Alternatively, it has been recognized to be one of the most promising drugs in a variety of pathophysiological disorders, such as inflammatory and neurodegenerative diseases, glioma, and cardiac failure [ 1 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]…”

MicroRNA-132 attenuated cardiac fibrosis in myocardial infarction-induced heart failure rats

“…The cardiac function was reduced in MI-induced heart failure rats [ 27 ], mice [ 28 , 29 ], rabbits [ 30 ], and swines [ 31 ]. In the present study, the results showed that the EF and FS of LV in MI-induced heart failure rats were reduced, which were improved by miR-132 agomiR.…”