Marchi Katia Colombo, Ceron Carla Speroni, Muniz Jaqueline J, De Martinis Bruno S, Tanus-Santos José E, Tirapelli Carlos Renato
Departamento de Farmacologia da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, USP, Ribeirão Preto, São Paulo, Brazil.
Alcohol Alcohol. 2016 Sep;51(5):522-34. doi: 10.1093/alcalc/agw043. Epub 2016 Jul 5.
Investigate the role of NADPH oxidase on ethanol-induced hypertension and vascular oxidative stress.
Male Wistar rats were treated with ethanol (20% v/v).
Apocynin (10 mg/kg/day, i.p.) prevented ethanol-induced hypertension. The increased contractility of endothelium-intact and endothelium-denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased superoxide anion (O2 (-)) generation and lipid peroxidation and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) or reduced glutathione (GSH). Ethanol did not alter the activities of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol increased the expression of Nox1, PKCδ, nNOS, SAPK/JNK and SOD2 in the rat aorta and apocynin prevented these responses. No difference on aortic expression of Nox2, Nox4, p47phox, Nox organizer 1 (Noxo1), eNOS and iNOS was detected after treatment with ethanol. Ethanol treatment did not alter the phosphorylation of SAPK/JNK, p38MAPK, c-Src, Rac1 or PKCδ.
The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to increased vascular Nox1/NADPH oxidase expression. This mechanism is involved in vascular dysfunction and hypertension induced by ethanol. Additionally, we conclude that ethanol consumption induces the expression of different proteins that regulate vascular contraction and growth and that NADPH oxidase-derived ROS play a role in such response.
The key findings of our study are that ethanol-induced hypertension is mediated by NADPH oxidase. Moreover, increased vascular Nox1 expression is related to the generation of reactive oxygen species (ROS) by ethanol. Finally, ROS induced by ethanol increase the expression of the regulatory vascular proteins.
研究NADPH氧化酶在乙醇诱导的高血压和血管氧化应激中的作用。
用乙醇（20% v/v）处理雄性Wistar大鼠。
阿朴吗啡（10 mg/kg/天，腹腔注射）可预防乙醇诱导的高血压。阿朴吗啡可预防乙醇处理大鼠完整内皮和去内皮主动脉环对去氧肾上腺素收缩性的增加。乙醇摄入增加超氧阴离子（O2 (-)）生成和脂质过氧化，而阿朴吗啡可预防这些反应。阿朴吗啡不能预防乙醇诱导的血浆和血管硝酸盐/亚硝酸盐（NOx）水平降低。乙醇处理不影响主动脉过氧化氢（H2O2）水平或还原型谷胱甘肽（GSH）水平。乙醇不改变黄嘌呤氧化酶（XO）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性。乙醇增加大鼠主动脉中Nox1、PKCδ、nNOS、SAPK/JNK和SOD2的表达，而阿朴吗啡可预防这些反应。乙醇处理后，未检测到主动脉中Nox2、Nox4、p47phox、Nox组织因子1（Noxo1）、eNOS和iNOS表达的差异。乙醇处理不改变SAPK/JNK、p38MAPK、c-Src、Rac1或PKCδ的磷酸化。
我们研究的主要新发现是，乙醇诱导的血管活性氧（ROS）生成增加与血管Nox1/NADPH氧化酶表达增加有关。该机制参与乙醇诱导的血管功能障碍和高血压。此外，我们得出结论，乙醇摄入诱导调节血管收缩和生长的不同蛋白质表达，且NADPH氧化酶衍生的ROS在此反应中起作用。
我们研究的关键发现是，乙醇诱导的高血压由NADPH氧化酶介导。此外，血管Nox1表达增加与乙醇诱导的活性氧（ROS）生成有关。最后，乙醇诱导的ROS增加调节血管的蛋白质表达。
Zotero 插件