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Reduced NAD(P)H oxidase in low renin hypertension: link among angiotensin II, atherogenesis, and blood pressure
- Source :
- Hypertension (Dallas, Tex. : 1979). 47(1)
- Publication Year :
- 2005
-
Abstract
- 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. gp91 phox , 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 gp91 phox . 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 p47 phox with gp91 phox 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.
- Subjects :
- medicine.medical_specialty
Endothelium
Systole
Vasodilator Agents
Blood Pressure
In Vitro Techniques
Left ventricular hypertrophy
Nitric oxide
chemistry.chemical_compound
Mice
Internal medicine
Renin–angiotensin system
Renin
Internal Medicine
medicine
Animals
Vasoconstrictor Agents
RNA, Messenger
Endothelial dysfunction
Sodium Chloride, Dietary
Aorta
Chemokine CCL2
Mice, Knockout
Membrane Glycoproteins
Rats, Inbred Dahl
Dose-Response Relationship, Drug
Chemistry
Angiotensin II
Osmolar Concentration
NADPH Oxidases
medicine.disease
Atherosclerosis
Scavenger Receptors, Class E
Acetylcholine
Rats
Vasodilation
Endocrinology
medicine.anatomical_structure
Blood pressure
NAD(P)H oxidase
Hypertension
NADPH Oxidase 2
Hypertrophy, Left Ventricular
Endothelium, Vascular
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 47
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....8bae8c163915358344ef9079b5a4c546