Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension.
Am J Hypertens
; 21(1): 72-7, 2008 Jan.
Article
en En
| MEDLINE
| ID: mdl-18091747
BACKGROUND: Angiotensin II (Ang II) receptor blocker (ARB) has been reported to have protective effects on the cardiovascular system independent of blood pressure reduction. Endothelial progenitor cells (EPCs) play a significant role in neovascularization of ischemic tissue. The average lifespan of EPCs was recently reported to be shortened by oxidative stress and regulated by anti-oxidative mechanisms. It has been reported that EPCs are present in peripheral blood and have the ability to repair cardiovascular damage. We investigated the effects of an ARB, candesartan, on EPC function and cardiovascular oxidation in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHR-SP) in vivo. METHODS: Salt-loaded SHR-SP were treated with candesartan (1 mg/kg/day), a diuretic (trichlormethiazide, TCM, 1.6 mg/kg/day), or an antioxidant (tempol, 5 mg/kg/day) for 2 weeks. Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation and migration. Oxidative stress in EPCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay. We evaluated messenger RNA (mRNA) expression of c-kit in the heart, the renin-angiotensin system (RAS) in EPC colonies, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit in cardiovascular organs. RESULTS: Candesartan and tempol, but not TCM, markedly increased EPC colony number in SHR-SP and reduced TBARS. Candesartan also significantly decreased mRNA expression of NADPH oxidase subunits in cardiovascular organs and increased cardiac c-kit mRNA expression. EPCs expressed mRNAs of renin, cathepsin D, chymase, and Ang II type 1 and type 2 receptors. CONCLUSIONS: Candesartan, an ARB, improves EPC dysfunction and increases cardiac c-kit expression through the anti-oxidative mechanism in hypertension. The local RAS induces oxidative stress and regulates the EPC functions.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre
/
Tetrazoles
/
Bencimidazoles
/
Estrés Oxidativo
/
Células Endoteliales
/
Bloqueadores del Receptor Tipo 1 de Angiotensina II
/
Hipertensión
/
Antihipertensivos
/
Antioxidantes
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Am J Hypertens
Asunto de la revista:
ANGIOLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos