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<p>The renin–angiotensin–aldosterone system (RAAS) is critical in ethanol-induced vascular dysfunction. Mineralocorticoid receptors (MR) trigger ethanol-induced vascular hypercontractility through pro-oxidative and pro-inflammatory effects. However, the contribution of MR to ethanol-induced perivascular adipose tissue (PVAT) dysfunction is unknown. Appreciating the importance of MR to PVAT dysfunction in distinctive pathological conditions, we investigated whether MR would play a role in ethanol-induced PVAT dysfunction. With this purpose, male Wistar <i>Hannover</i> rats were treated with ethanol 20% (in volume ratio) and/or potassium canrenoate [a MR antagonist (MRA); 30&#xa0;mg/kg/day, gavage] for 5&#xa0;weeks. Ethanol increased the circulating levels of aldosterone and impaired acetylcholine-induced relaxation of mesenteric arteries with, but not without PVAT. Antagonism of MR prevented ethanol-induced impairment in acetylcholine relaxation as well as the reduction of leptin levels and reactive oxygen species (ROS) overproduction in the mesenteric PVAT (mPVAT) from ethanol-treated rats. Ethanol promoted neutrophil accumulation and augmented the concentration of tumor necrosis factor (TNF)-α in the mPVAT and these responses were prevented by the MRA. Functional assays showed that tiron [a scavenger of superoxide (O<sub>2</sub><sup>•−</sup>)] and etanercept (an antibody anti-TNF-α) failed to reverse the impairment of acetylcholine-induced relaxation promoted by ethanol. In mesenteric arteries, antagonism of MR prevented ROS generation, lipoperoxidation, and increased TNF-α levels induced by ethanol. In conclusion, our findings suggest that MR is involved in ethanol-induced dysfunction of mPVAT. This study enhances our understanding of how ethanol exerts harmful effects on the cardiovascular system, highlighting PVAT as a target for these detrimental effects.</p>

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Ethanol-induced dysfunction of the mesenteric perivascular adipose tissue is driven by mineralocorticoid receptors

  • 期刊论文

  • 发表日期：

    2025年5月16日

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  • Ivis V. O. Martins,
  • Thales M. H. Dourado,
  • Gustavo F. Pimenta,
  • Marcela M. Blascke de Mello,
  • Aline G. Fedoce,
  • Wanessa M. C. Awata,
  • Michele M. Castro,
  • Rita C. Tostes,
  • Carlos R. Tirapelli

摘要

The renin–angiotensin–aldosterone system (RAAS) is critical in ethanol-induced vascular dysfunction. Mineralocorticoid receptors (MR) trigger ethanol-induced vascular hypercontractility through pro-oxidative and pro-inflammatory effects. However, the contribution of MR to ethanol-induced perivascular adipose tissue (PVAT) dysfunction is unknown. Appreciating the importance of MR to PVAT dysfunction in distinctive pathological conditions, we investigated whether MR would play a role in ethanol-induced PVAT dysfunction. With this purpose, male Wistar Hannover rats were treated with ethanol 20% (in volume ratio) and/or potassium canrenoate [a MR antagonist (MRA); 30 mg/kg/day, gavage] for 5 weeks. Ethanol increased the circulating levels of aldosterone and impaired acetylcholine-induced relaxation of mesenteric arteries with, but not without PVAT. Antagonism of MR prevented ethanol-induced impairment in acetylcholine relaxation as well as the reduction of leptin levels and reactive oxygen species (ROS) overproduction in the mesenteric PVAT (mPVAT) from ethanol-treated rats. Ethanol promoted neutrophil accumulation and augmented the concentration of tumor necrosis factor (TNF)-α in the mPVAT and these responses were prevented by the MRA. Functional assays showed that tiron [a scavenger of superoxide (O2•−)] and etanercept (an antibody anti-TNF-α) failed to reverse the impairment of acetylcholine-induced relaxation promoted by ethanol. In mesenteric arteries, antagonism of MR prevented ROS generation, lipoperoxidation, and increased TNF-α levels induced by ethanol. In conclusion, our findings suggest that MR is involved in ethanol-induced dysfunction of mPVAT. This study enhances our understanding of how ethanol exerts harmful effects on the cardiovascular system, highlighting PVAT as a target for these detrimental effects.