1. Tumor necrosis factor-α receptor 1 contributes to ethanol-induced vascular reactive oxygen species generation and hypertension.
- Author
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Simplicio JA, Gonzaga NA, Nakashima MA, De Martinis BS, Cunha TM, Tirapelli LF, and Tirapelli CR
- Subjects
- Adipose Tissue enzymology, Adipose Tissue pathology, Animals, Aorta pathology, Blood Pressure, Catalase metabolism, Humans, Hypertension etiology, Interleukin-6 metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxidative Stress, Peroxidase metabolism, Receptors, Tumor Necrosis Factor, Type I genetics, Superoxide Dismutase metabolism, Tumor Necrosis Factor-alpha metabolism, Aorta enzymology, Ethanol adverse effects, Hypertension pathology, Reactive Oxygen Species metabolism, Receptors, Tumor Necrosis Factor, Type I metabolism
- Abstract
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., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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