Thiazide diuretics, endothelial function, and vascular oxidative stress : Journal of Hypertension

Journal Logo

Original papers: Endothelium

Thiazide diuretics, endothelial function, and vascular oxidative stress

Zhou, Ming-Sheng; Schulman, Ivonne Hernandez; Jaimes, Edgar A; Raij, Leopoldo

Author Information
Journal of Hypertension 26(3):p 494-500, March 2008. | DOI: 10.1097/HJH.0b013e3282f3e39d



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.


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).


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.


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.

© 2008 Lippincott Williams & Wilkins, Inc.

You can read the full text of this article if you:

Access through Ovid