Perivascular adipose tissue protects against the vascular dysfunction induced by acute ethanol intake: Role of hydrogen peroxide

Vascul Pharmacol. 2018 Dec:111:44-53. doi: 10.1016/j.vph.2018.08.010. Epub 2018 Aug 26.

Abstract

Aim: We investigated the consequences of acute ethanol intake on the anti-contractile effect of perivascular adipose tissue (PVAT).

Methods: The effects of a single dose of ethanol (1 g/kg; p.o. gavage) on the vascular function were assessed within 30 min in male Wistar rats.

Results: Ethanol decreased the relaxation induced by acetylcholine and increased the contraction induced by phenylephrine in endothelium-intact, but not in endothelium-denuded aortas without PVAT. The vascular dysfunction induced by ethanol was not observed in aortic rings with PVAT. Nω-Nitro-l-arginine methyl ester (L-NAME), NG-nitro-l-arginine (L-NNA) and 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not tiron or tempol, increased the contraction induced by phenylephrine in endothelium-intact aortas with PVAT from control and ethanol-treated rats. Catalase increased phenylephrine-induced contraction in aortas with PVAT from ethanol-treated rats, but not from control rats. Conversely, inhibition of catalase with aminotriazole decreased phenylephrine-induced contraction in aortas from ethanol-treated rats. Treatment with ethanol increased hydrogen peroxide (H2O2) levels and decreased catalase activity in aortas with PVAT. Ethanol increased superoxide anion (O2-) generation in aortas with or without PVAT. Superoxide dismutase (SOD) activity was not affected by ethanol intake. In situ quantification of H2O2 using 2'7'dichlorodihydrofluorescein diacetate (DCFH-DA) revealed increased levels of H2O2 in periaortic PVAT from ethanol-treated rats. However, in situ evaluation of nitric oxide (NO) in both aorta and PVAT showed no differences between groups.

Conclusions: Our study provides novel evidence that the periaortic PVAT protects against the vascular dysfunction induced by acute ethanol intake through a mechanism that involves increased generation of H2O2.

Keywords: Endothelial dysfunction; Ethanol; Hydrogen peroxide; Perivascular adipose tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiopathology
  • Animals
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / physiopathology
  • Catalase / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Ethanol / administration & dosage
  • Ethanol / toxicity*
  • Hydrogen Peroxide / metabolism*
  • Male
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism
  • Up-Regulation
  • Vasoconstriction / drug effects*
  • Vasodilation / drug effects*

Substances

  • Superoxides
  • Ethanol
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase