Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors
Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors
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DOI：
10.1016/j.ejphar.2008.04.044
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发表时间：
2008-07-07
影响因子：
5
通讯作者：
Albino-Teixeira, Antonio
中科院分区：
文献类型：
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作者：
Sousa, Teresa;Pinho, Dora;Albino-Teixeira, Antonio
用腺苷受体拮抗剂1,3-二丙基-8-磺苯基黄嘌呤（DPSPX）治疗Wistar大鼠7天，可诱导与血管结构、反应性和肾素-血管紧张素系统激活显著变化相关的长期高血压。本研究旨在评估氧化应激在dpspx诱导的高血压发展中的作用，并确定超氧自由基（O-2（中心点-））与过氧化氢（H2O2）的相对贡献。对假手术（生理盐水，ig， 7天）和DPSPX （90 μ g/kg/h, ig， 7天）大鼠血管和全身促氧化/抗氧化状态进行评估。采用有创和无创方法测定收缩压。采用荧光/分光光度法测定血管内NADPH氧化酶、超氧化物歧化酶（SOD）、过氧化氢酶和谷胱甘肽过氧化物酶的活性。使用Amplex Red过氧化氢试剂盒测定H2O2水平。同时测定血浆硫代巴比妥酸活性物质和血浆抗氧化能力。此外，我们还测试了抗氧化剂或活性氧生成抑制剂对血压、血管增生和氧化应激参数的影响。dpspx高血压大鼠血管NADPH氧化酶、SOD、过氧化氢酶和谷胱甘肽过氧化物酶活性升高，H2O2生成增加。dpspx高血压大鼠血浆脂质过氧化增加，血浆抗氧化能力下降。用apocypin （1.5 mmol/l，每天14天）或聚乙二醇过氧化氢酶（10,000 U/kg/天，每天1次，8天）处理，可以阻止dpspx诱导的血压、血管结构和H2O2水平的影响。Tempol （3 mmol/l / s， 14天）不能抑制这些变化，除非同时给药peg -过氧化氢酶。由此可见，O-2（中心点-）的生成和随后H2O2的形成在dpspx诱导的高血压的发展中起主要作用。(C) 2008 Elsevier B.V.版权所有
Treatment of Wistar rats for 7 days with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, induces long-lasting hypertension associated with marked changes in vascular structure and reactivity and renin-angiotensin system activation. This study aimed at evaluating the role of oxidative stress in the development of DPSPX-induced hypertension and also at identifying the relative contribution of superoxide radical (O-2(center dot-)) vs hydrogen peroxide (H2O2). Vascular and systemic prooxidant/antioxidant status was evaluated in sham (saline, i.p., 7 days) and DPSPX (90 mu g/kg/h, i.p., 7 days)-treated rats. Systolic blood pressure was determined by invasive and non-invasive methods. The activity of vascular NADPH oxidase, superoxide dismutase (SOD), catalase and glutathione peroxidase was assayed by fluorometric/spectro-photometric methods. H2O2 levels were measured using an Amplex Red Hydrogen Peroxide kit. Plasma thiobarbituric acid reactive substances and plasma antioxidant capacity were also measured. In addition we tested the effects of antioxidants or inhibitors of reactive oxygen species generation on blood pressure, vascular hyperplasia and oxidative stress parameters. DPSPX-hypertensive rats showed increased activity of vascular NADPH oxidase, SOD, catalase and glutathione peroxidase, as well as increased H2O2 generation. DPSPX-hypertensive rats also had increased plasma lipid peroxidation and decreased plasma antioxidant capacity. Treatment with apocypin (1.5 mmol/l, per os, 14 days), or with polyethylene glycol (PEG)-catalase (10,000 U/kg/day, i.p., 8 days), prevented the DPSPX-induced effects on blood pressure, vascular structure and H2O2 levels. Tempol (3 mmol/l, per os, 14 days) failed to inhibit these changes, unless PEG-catalase was co-administered. It is concluded that O-2(center dot-) generation with subsequent formation of H2O2 plays a major role in the development of DPSPX-induced hypertension. (C) 2008 Elsevier B.V. All rights reserved.