Carotid baroreceptor stimulation prevents oxidative stress by inhibiting MAO-A and prevents cardiac remodeling in obese rats

Obesity (Silver Spring). 2023 Jun;31(6):1620-1633. doi: 10.1002/oby.23729. Epub 2023 Mar 30.

Abstract

Objective: Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor stimulation (CBS) on cardiac remodeling in obese rats and the underlying mechanisms were explored.

Methods: An obesity model was induced by 16-week high-fat diet feeding. A CBS device was implanted at the 8th week. Body weight and blood pressure measurements, electrocardiography, echocardiography, and glucose and insulin tolerance tests were conducted before sampling. Plasma analysis and histological and biological analyses of left ventricle were also performed. Neonatal rat cardiomyocytes cocultured with 3T3-L1 in transwell chambers were used to investigate the mechanisms.

Results: CBS alleviated several manifestations of obesity, including increased body weight, high blood pressure, hyperlipidemia, and enhanced sympathetic activity. In obese hearts, norepinephrine levels decreased, and the monoamine oxidase A (MAO-A) and reactive oxygen species level increased; these changes, as well as cardiac fibrosis, lipid metabolic disorders, and heart dysfunction, were inhibited by CBS. Neonatal rat cardiomyocytes incubated with norepinephrine showed MAO-A upregulation, increased reactive oxygen species levels, lipid metabolic disorders, and inflammatory response, which were inhibited by clorgyline, a selective MAO-A inhibitor.

Conclusions: CBS effectively suppresses sympathetic nervous system activity and oxidative stress mediated by MAO-A and prevents cardiac remodeling in obese rats.

MeSH terms

  • Animals
  • Lipids
  • Monoamine Oxidase* / metabolism
  • Monoamine Oxidase* / pharmacology
  • Norepinephrine / pharmacology
  • Obesity / pathology
  • Oxidative Stress
  • Pressoreceptors* / metabolism
  • Pressoreceptors* / pathology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology
  • Ventricular Remodeling

Substances

  • Monoamine Oxidase
  • Reactive Oxygen Species
  • Lipids
  • Norepinephrine