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

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. N ω -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 (H 2 O 2 ) levels and decreased catalase activity in aortas with PVAT. Ethanol increased superoxide anion (O 2 − ) generation in aortas with or without PVAT. Superoxide dismutase (SOD) activity was not affected by ethanol intake. In situ quantification of H 2 O 2 using 2′7′dichlorodihydrofluorescein diacetate (DCFH-DA) revealed increased levels of H 2 O 2 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 H 2 O 2 .