Hydrogen peroxide mediates endothelium-dependent dilation of coronary arterioles in obese rats on a low-carbohydrate diet

Microcirculation. 2013 Oct;20(7):599-608. doi: 10.1111/micc.12058.

Abstract

Objective: Endothelium-dependent vasodilation of coronary arterioles is impaired in obese rats and may be improved by a LCD. The aim of this study is to elucidate the mechanism by which this improvement occurs.

Methods: We used four groups of male Zucker rats: lean and obese on either SD or LCD. Coronary arterioles were cannulated and pressurized for diameter measurements during administration of acetylcholine or sodium nitroprusside or during flow. Real-time PCR was performed to quantify mRNA expression of CuZnSOD and catalase.

Results: The LCD significantly increased endothelium-dependent dilation in the obese rats. l-NAME and indomethacin reduced responses to flow and acetylcholine in the lean rats without any effect on the obese on either diet. In contrast, TEA and catalase blocked flow-dependent and acetylcholine-induced dilation in the obese on either diet, while no effect was observed on the lean. The LCD in the obese significantly up-regulated catalase mRNA expression and slightly increased CuZnSOD mRNA levels.

Conclusions: A LCD improves endothelium-dependent vasodilation of coronary arterioles in obese rats through the production of H2 O2 which acts as a hyperpolarizing factor, independent of nitric oxide and PGI2 .

Keywords: coronary arterioles; endothelium dysfunction; low-carbohydrate diet; obesity.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Arterioles / metabolism
  • Arterioles / parasitology
  • Arterioles / pathology
  • Coronary Circulation / drug effects*
  • Dietary Carbohydrates / pharmacology*
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / pathology
  • Endothelium, Vascular* / physiopathology
  • Enzyme Inhibitors / pharmacology
  • Hydrogen Peroxide / metabolism*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitroprusside / pharmacology
  • Obesity* / diet therapy
  • Obesity* / metabolism
  • Obesity* / pathology
  • Obesity* / physiopathology
  • Rats
  • Rats, Zucker
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology

Substances

  • Dietary Carbohydrates
  • Enzyme Inhibitors
  • Vasodilator Agents
  • Nitroprusside
  • Hydrogen Peroxide
  • Acetylcholine
  • NG-Nitroarginine Methyl Ester