Document Detail

Reduced NAD(P)H oxidase in low renin hypertension: link among angiotensin II, atherogenesis, and blood pressure.
MedLine Citation:
PMID:  16344366     Owner:  NLM     Status:  MEDLINE    
Endothelial dysfunction (ED) complicates hypertension and is a precursor of atherosclerosis. Reduced NO bioactivity, because of increased reduced NAD(P)H oxidase-derived reactive oxygen species (ROS), plays a critical role in ED. gp91phox, predominantly expressed in the endothelium and adventitia, is a subunit of NAD(P)H oxidase important for its activation in response to angiotensin (Ang) II. Human atherosclerotic plaques are heavy laden with gp91phox. We have shown that in Dahl salt-sensitive (DS) rats, a paradigm of low renin salt-sensitive (SS) hypertension in humans, Ang II receptor blockade normalizes ROS production and endothelium-dependent relaxation (EDR) without significantly affecting systolic blood pressure (SBP). To additionally elucidate the mechanisms involved in the functional association of Ang II in SS hypertension, we administered a cell-permeable inhibitor of the assembly of p47phox with gp91phox in NAD(P)H oxidase, gp91ds-tat (10 mg/kg body weight, 3 weeks by minipump), to DS rats fed a 4% salt diet. Control rats received either vehicle or an inactive scramb-tat peptide. Vehicle-treated DS developed hypertension (SBP 168+/-5 mm Hg), left ventricular hypertrophy (LVH), proteinuria, impaired EDR, and increased aortic ROS production (superoxide 115% and peroxynitrite 157%) and expression of the proatherogenic molecules LOX-1 (130%) and MCP-1 (166%). gp91ds-tat, but not scramb-tat, normalized ROS and EDR, as well as LOX-1 and MCP-1, despite nonsignificant effects on SBP (159+/-5 mm Hg; P>0.05), left ventricular hypertrophy, and proteinuria. Our findings support the notion that in SS hypertension, activation of NAD(P)H oxidase promotes ED and atherogenesis via decreased nitric oxide bioactivity and increased LOX-1 and MCP-1, independent of blood pressure.
Ming-Sheng Zhou; Ivonne Hernandez Schulman; Patrick J Pagano; Edgar A Jaimes; Leopoldo Raij
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2005-12-12
Journal Detail:
Title:  Hypertension     Volume:  47     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-23     Completed Date:  2006-01-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  81-6     Citation Subset:  IM    
Veterans Affairs Medical Center, Division of Nephrology and Hypertension, Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
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MeSH Terms
Acetylcholine / pharmacology
Angiotensin II / metabolism*,  pharmacology
Aorta / drug effects,  metabolism
Atherosclerosis / etiology*
Blood Pressure* / drug effects
Chemokine CCL2 / genetics
Dose-Response Relationship, Drug
Endothelium, Vascular / physiopathology
Hypertension / blood,  enzymology,  metabolism*,  physiopathology
Hypertrophy, Left Ventricular / chemically induced
Membrane Glycoproteins / deficiency
Mice, Knockout
NADPH Oxidase / deficiency,  metabolism*
Osmolar Concentration
RNA, Messenger / metabolism
Rats, Inbred Dahl
Renin / blood*
Scavenger Receptors, Class E / genetics
Sodium Chloride, Dietary / administration & dosage,  pharmacology
Vasoconstrictor Agents / metabolism*,  pharmacology
Vasodilator Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Ccl2 protein, rat; 0/Chemokine CCL2; 0/Membrane Glycoproteins; 0/Oldlr1 protein, rat; 0/RNA, Messenger; 0/Scavenger Receptors, Class E; 0/Sodium Chloride, Dietary; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 51-84-3/Acetylcholine; EC protein, mouse; EC Oxidase; EC

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