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NADPH oxidase contributes to the left ventricular dysfunction induced by sinoaortic denervation in rats
1First Geriatric Cardiology Department, Chinese PLA General Hospital , Beijing , P. R. China.
Abstract:
The aim of this work was to investigate the role nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on left ventricular dysfunction of rats submitted to sinoaortic denervation (SAD). Experiment 1: 8 weeks after SAD of rats, NADPH oxidase in left ventricles was assayed by Western blotting analysis. Experiment 2: Rats were subjected to SAD and received treatment with apocynin (an NADPH oxidase inhibitor, 30 mg/kg/day, intragastric administration) for 8 weeks; 8 weeks after SAD, Nox2 and Nox4 expressions and Rac1 activity of left ventricles were higher in SAD rats than those in sham-operated rats. Although treatment of SAD rats with apocynin did not affect blood pressure, blood pressure variability (BPV), and baroreflex function, it significantly attenuated left ventricular hypertrophy marked by reduced expression of atrial natriuretic factor and β-myosin heavy chain. Treatment of SAD rats with apocynin abated oxidative stress marked by reduced malondialdehyde formation and suppressed nuclear factor-kappa B (NFκB) activation; inflammation marked by reduced monocyte chemoattractant protein-1 expression and myeloperoxidase activity; attenuated endoplasmic reticulum stress marked by reduced expression of CCAAT-enhancer-binding protein homologous protein, chaperone-glucose-regulated protein 78, and X-box protein 1; and alleviated cardiac fibrosis marked by reduced mRNA levels of collagens I and III and transforming growth factor beta. In conclusion, exaggerated BPV induces chronic myocardial oxidative stress and thereby aggravates cardiac remodeling in rats. These data suggest a potential role of NADPH oxidases in the pathogenesis of cardiac dysfunction induced by exaggerated BPV.
Insights
Sinoaortic denervation in rats increases NADPH oxidase activity, leading to cardiac dysfunction. Inhibiting NADPH oxidase with apocynin reduces oxidative stress and cardiac remodeling, suggesting a therapeutic target for heart disease.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Pharmacology
Background:
- Sinoaortic denervation (SAD) disrupts baroreflex control, leading to altered blood pressure variability (BPV).
- NADPH oxidase (NOX) is implicated in oxidative stress and cardiovascular disease.
Purpose of the Study:
- To investigate the role of NADPH oxidase in left ventricular dysfunction following sinoaortic denervation in rats.
- To evaluate the therapeutic potential of apocynin, an NADPH oxidase inhibitor, in mitigating SAD-induced cardiac changes.
Main Methods:
- Rats underwent sinoaortic denervation (SAD) or sham surgery.
- NADPH oxidase activity, Nox2/Nox4 expression, and Rac1 activity were assessed.
- Apocynin treatment was administered to SAD rats.
- Cardiac hypertrophy, oxidative stress, inflammation, endoplasmic reticulum stress, and fibrosis markers were analyzed.
Main Results:
- SAD increased Nox2, Nox4 expression, and Rac1 activity in the left ventricle.
- Apocynin treatment attenuated left ventricular hypertrophy, oxidative stress, inflammation, ER stress, and cardiac fibrosis without altering blood pressure or baroreflex function.
- Apocynin reduced malondialdehyde, NFκB activation, MCP-1, MPO activity, and markers of ER stress and fibrosis.
Conclusions:
- Exaggerated blood pressure variability post-SAD induces chronic myocardial oxidative stress, aggravating cardiac remodeling.
- NADPH oxidase plays a significant role in the pathogenesis of cardiac dysfunction induced by exaggerated BPV.
