Melatonin reverses the loss of the anticontractile effect of perivascular adipose tissue in obese rats

J Pineal Res. 2021 Mar;70(2):e12710. doi: 10.1111/jpi.12710. Epub 2020 Dec 26.

Abstract

Perivascular adipose tissue (PVAT) undergoes functional changes in obesity. Increased oxidative stress is a central mechanism whereby obesity induces loss of the anticontractile effect of PVAT. Melatonin is an antioxidant that displays vasoprotective action in cardiovascular disease. Here, we sought to investigate whether melatonin would restore the anticontractile effect of periaortic PVAT in obesity. Male Wistar Hannover rats were treated for 10 weeks with a high-calorie diet. Melatonin (5 mg/kg/d, p.o., gavage) was administered for 2 weeks. Functional findings showed that obesity-induced loss of the anticontractile effect of PVAT and treatment with melatonin reversed this response. Tiron [a scavenger of superoxide anion (O2 - )] restored the anticontractile effect of PVAT in aortas from obese rats, suggesting a role for reactive oxygen species (ROS) in such response. Decreased superoxide dismutase (SOD) activity and augmented levels of ROS were detected in periaortic PVAT from obese rats. These responses were accompanied by decreased levels of nitric oxide (NO) in PVAT. Treatment with melatonin restored SOD activity, decreased ROS levels, and increased NO bioavailability in PVAT from obese rats. Here, we first reported the beneficial effects of melatonin in periaortic PVAT in obesity. Melatonin reversed the adverse effects of obesity in PVAT that included overproduction of ROS, reduced SOD activity, and decreased bioavailability of NO. Therefore, PVAT may constitute an important target for the treatment of obesity-induced vascular dysfunction and melatonin emerges as a potential tool in the management of the vascular complications induced by obesity.

Keywords: aorta; melatonin; nitric oxide; obesity; perivascular adipose tissue; reactive oxygen species; vascular dysfunction.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Male
  • Melatonin / therapeutic use*
  • Obesity / drug therapy*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Melatonin