Thiazide diuretics, endothelial function, and vascular oxidative stress.
Thiazide diuretics, endothelial function, and vascular oxidative stress.
复制标题
噻嗪类利尿剂、内皮功能和血管氧化应激。
DOI：
10.1097/hjh.0b013e3282f3e39d
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发表时间：
2008
影响因子：
4.9
通讯作者：
Raij,Leopoldo
中科院分区：
文献类型：
--
作者：
Zhou,Ming-Sheng;Schulman,IvonneHernandez;Jaimes,EdgarA;Raij,Leopoldo
目的：高血压与动脉粥样硬化的发生密切相关，高血压患者内皮细胞活性氧的产生增加，一氧化氮的生物活性降低，单核细胞趋化蛋白（MCP）-1和凝集素样氧化低密度脂蛋白受体（LOX）-1表达上调。我们研究了噻嗪类利尿剂的有益作用是否仅与降低高血压的生物力学应激有关，或者是否也具有与其对血压的作用无关的多效性血管保护作用。方法Dahl盐敏感（DSS）大鼠，人类盐敏感性高血压的范例，给予正常盐的饮食（0.5%NaCl）、高盐（4%NaCl）或高盐饮食加氢氯噻嗪75 mg/l、氯噻酮37或75 mg/l（饮用水），持续6周。我们测定了收缩压（SBP）、左心室肥大（LVH）、蛋白尿、主动脉超氧阴离子（O2 −）产生、乙酰胆碱内皮依赖性舒张（EDR）、主动脉血管紧张素II 1型（AT 1）受体、LOX-1和MCP-1信使RNA表达结果高盐饮食的DSS大鼠出现高血压、LVH、蛋白尿、主动脉O2-生成增加（106%）、EDR受损，主动脉AT 1受体、LOX 1和MCP 1表达上调率分别为198%、135%和145%。氢氯噻嗪以及高剂量和低剂量的氯噻酮降低SBP，LVH和蛋白尿，但没有减少O2-生产，AT 1受体，LOX-1，或MCP-1的表达，或改善EDR.ConclusionsThis研究表明，噻嗪类利尿剂不降低氧化应激，改善内皮功能，或防止促动脉粥样硬化分子的表达。我们的结论是噻嗪类利尿剂可能不能完全提供长期的全球心血管保护超越降低血压。
ObjectivesIncreased endothelial production of reactive oxygen species and decreased nitric oxide bioactivity, associated with the upregulation of monocyte chemoattractant protein (MCP)-1 and lectin-like oxidized low-density lipoprotein receptor (LOX)-1, link hypertension with atherogenesis. We investigated whether the beneficial effects of thiazide diuretics are exclusively related to a reduction in the biomechanical stress of hypertension or are also endowed with pleiotropic vasculoprotective effects that are independent of their effect upon blood pressure.MethodsDahl salt-sensitive (DSS) rats, a paradigm of human salt-sensitive hypertension, were given a diet with normal salt (0.5% NaCl), high salt (4% NaCl), or a high salt diet plus either hydrochlorothiazide 75 mg/l, chlorthalidone 37 or 75 mg/l in their drinking water for 6 weeks. We determined systolic blood pressure (SBP), left ventricular hypertrophy (LVH), proteinuria, aortic superoxide anion (O 2−) production, endothelium-dependent relaxation (EDR) to acetylcholine, and aortic angiotensin II type 1 (AT 1) receptor, LOX-1, and MCP-1 messenger RNA expression (by real-time polymerase chain reaction).ResultsDSS rats on a high salt diet developed hypertension, LVH, proteinuria, increased production of aortic O 2−(106%), impaired EDR, and aortic upregulation of AT 1 receptor (198%), LOX-1 (135%), and MCP-1 (145%). Hydrochlorothiazide as well as the high and low dose of chlorthalidone reduced SBP, LVH, and proteinuria, but did not reduce O 2− production, AT 1 receptor, LOX-1, or MCP-1 expression, or improved EDR.ConclusionsThis study demonstrates that thiazide diuretics do not reduce oxidative stress, improve endothelial function, or prevent the expression of pro-atherogenic molecules. We conclude that thiazide diuretics may not fully provide long-term global cardiovascular protection beyond lowering blood pressure.