NADPH oxidase contributes to the left ventricular dysfunction induced by sinoaortic denervation in rats.

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.
AuthorsL Zhang, F Li, G Zhi, B Zhang, Y-D Chen
JournalFree radical research (Free Radic Res) Vol. 49 Issue 1 Pg. 57-66 (Jan 2015) ISSN: 1029-2470 [Electronic] England
PMID25356862 (Publication Type: Journal Article)
Chemical References
  • Acetophenones
  • Enzyme Inhibitors
  • acetovanillone
  • NADPH Oxidase
  • Acetophenones (pharmacology)
  • Animals
  • Autonomic Denervation
  • Endoplasmic Reticulum Stress (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Heart Ventricles (drug effects)
  • Hypertrophy, Left Ventricular (enzymology, etiology)
  • Male
  • NADPH Oxidase (antagonists & inhibitors, metabolism)
  • Oxidative Stress (drug effects, physiology)
  • Rats
  • Rats, Sprague-Dawley
  • Sinus of Valsalva (innervation)

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