Thiazide diuretics, endothelial function, and vascular oxidative stress

Ming Sheng Zhou, Ivonne H Schulman, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)494-500
Number of pages7
JournalJournal of Hypertension
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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Sodium Chloride Symporter Inhibitors
Blood Vessels
Oxidative Stress
Chemokine CCL2
Blood Pressure
Salts
Angiotensin Type 1 Receptor
Left Ventricular Hypertrophy
Proteinuria
Chlorthalidone
Inbred Dahl Rats
Hypertension
Endothelium
Hydrochlorothiazide
Diet
Class E Scavenger Receptors
Up-Regulation
Superoxides
Drinking Water
Acetylcholine

Keywords

  • Antihypertensive drugs
  • Basic science
  • Cardiovascular disease
  • Endothelium
  • Oxidant stress

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Thiazide diuretics, endothelial function, and vascular oxidative stress. / Zhou, Ming Sheng; Schulman, Ivonne H; Jaimes, Edgar A.; Raij, Leopoldo.

In: Journal of Hypertension, Vol. 26, No. 3, 01.03.2008, p. 494-500.

Research output: Contribution to journalArticle

Zhou, Ming Sheng ; Schulman, Ivonne H ; Jaimes, Edgar A. ; Raij, Leopoldo. / Thiazide diuretics, endothelial function, and vascular oxidative stress. In: Journal of Hypertension. 2008 ; Vol. 26, No. 3. pp. 494-500.
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T1 - Thiazide diuretics, endothelial function, and vascular oxidative stress

AU - Zhou, Ming Sheng

AU - Schulman, Ivonne H

AU - Jaimes, Edgar A.

AU - Raij, Leopoldo

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Y1 - 2008/3/1

N2 - 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.

AB - 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.

KW - Antihypertensive drugs

KW - Basic science

KW - Cardiovascular disease

KW - Endothelium

KW - Oxidant stress

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