We evaluated the contribution of tumor necrosis factor-α receptor 1 (TNFR1) to ethanol-induced hypertension and vascular oxidative stress and the possible role of perivascular adipose tissue (PVAT) in such responses. Male C57BL/6 wild-type (WT) or TNFR1-deficient mice (TNFR1-/-) were treated with ethanol (20% vol/vol) for 12 weeks. Ethanol induced an increase in blood pressure in WT mice and TNFR1-/- at 4 and 5 weeks of treatment, respectively. Treatment with ethanol increased tumor necrosis factor-α and interleukin-6 levels in aortas with or without PVAT (PVAT+ and PVAT-, respectively) from WT mice, but not TNFR1-/-. Ethanol increased superoxide anion (O2-) generation, thiobarbituric acid reactive substance concentration, and the activity of superoxide dismutase and catalase in aortas (PVAT- and PVAT+) from WT mice, but not TNFR1-/-. Conversely, ethanol consumption decreased the concentration of nitrate/nitrite in aortas (PVAT- and PVAT+) from WT mice, but not TNFR1-/-. Treatment with ethanol increased myeloperoxidase activity in aortas (PVAT- and PVAT+) from WT mice, but not TNFR1-/-. The major finding of our study is that TNFR1 contributes to ethanol-induced hypertension and oxidative stress in the vasculature. Additionally, TNFR1 plays a role in ethanol-induced increase in proinflammatory cytokines and neutrophils migration. However, PVAT does not counteract or aggravate the effects induced by ethanol.

中文翻译：

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肿瘤坏死因子-α受体1有助于乙醇诱导的血管活性氧的产生和高血压。

我们评估了肿瘤坏死因子-α受体1（TNFR1）对乙醇诱导的高血压和血管氧化应激的贡献，以及血管周围脂肪组织（PVAT）在此类反应中的可能作用。雄性C57BL / 6野生型（WT）或TNFR1缺陷小鼠（TNFR1-/-）用乙醇（20％vol / vol）处理12周。乙醇分别在治疗的4周和5周时引起WT小鼠和TNFR1-/-的血压升高。用乙醇治疗可增加或不引起野生型小鼠的PVAT（分别为PVAT +和PVAT-），但TNFR1-/-则增加主动脉中的肿瘤坏死因子-α和白介素6水平。乙醇可增加野生型小鼠的主动脉中超氧阴离子（O2-）的生成，硫代巴比妥酸反应物的浓度以及超氧化物歧化酶和过氧化氢酶的活性，而TNFR1-/-则不。反过来，乙醇消耗降低了野生型小鼠的主动脉（PVAT-和PVAT +）中硝酸盐/亚硝酸盐的浓度，但未降低TNFR1-/-。用乙醇处理可增加野生型小鼠的主动脉（PVAT-和PVAT +）中的髓过氧化物酶活性，但不会增加TNFR1-/-。我们研究的主要发现是TNFR1有助于乙醇诱发的高血压和血管系统的氧化应激。此外，TNFR1在乙醇诱导的促炎性细胞因子和中性粒细胞迁移增加中发挥作用。但是，PVAT不能抵消或加剧乙醇引起的影响。我们研究的主要发现是TNFR1有助于乙醇诱发的高血压和血管系统的氧化应激。此外，TNFR1在乙醇诱导的促炎性细胞因子和中性粒细胞迁移增加中发挥作用。但是，PVAT不能抵消或加剧乙醇引起的影响。我们研究的主要发现是TNFR1有助于乙醇诱发的高血压和血管系统的氧化应激。此外，TNFR1在乙醇诱导的促炎性细胞因子和中性粒细胞迁移增加中发挥作用。但是，PVAT不能抵消或加剧乙醇引起的影响。