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Thiazide diuretics, endothelial function, and vascular oxidative stress.

Abstract：

OBJECTIVES:Increased 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. METHODS:Dahl 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 (O2(-)) production, endothelium-dependent relaxation (EDR) to acetylcholine, and aortic angiotensin II type 1 (AT1) receptor, LOX-1, and MCP-1 messenger RNA expression (by real-time polymerase chain reaction). RESULTS:DSS rats on a high salt diet developed hypertension, LVH, proteinuria, increased production of aortic O2(-) (106%), impaired EDR, and aortic upregulation of AT1 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 O2(-) production, AT1 receptor, LOX-1, or MCP-1 expression, or improved EDR. CONCLUSIONS:This 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.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Zhou MS,Schulman IH,Jaimes EA,Raij L

doi

10.1097/HJH.0b013e3282f3e39d

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

494-500

issue

eissn

0263-6352

issn

1473-5598

pii

00004872-200803000-00018

journal_volume

pub_type

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Thiazide diuretics, endothelial function, and vascular oxidative stress.