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Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension.
Am J Hypertens. 2008 Jan; 21(1):72-7.AJ

Abstract

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.

Authors+Show Affiliations

Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18091747

Citation

Yu, Yi, et al. "Effects of an ARB On Endothelial Progenitor Cell Function and Cardiovascular Oxidation in Hypertension." American Journal of Hypertension, vol. 21, no. 1, 2008, pp. 72-7.
Yu Y, Fukuda N, Yao EH, et al. Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension. Am J Hypertens. 2008;21(1):72-7.
Yu, Y., Fukuda, N., Yao, E. H., Matsumoto, T., Kobayashi, N., Suzuki, R., Tahira, Y., Ueno, T., & Matsumoto, K. (2008). Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension. American Journal of Hypertension, 21(1), 72-7.
Yu Y, et al. Effects of an ARB On Endothelial Progenitor Cell Function and Cardiovascular Oxidation in Hypertension. Am J Hypertens. 2008;21(1):72-7. PubMed PMID: 18091747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension. AU - Yu,Yi, AU - Fukuda,Noboru, AU - Yao,En-Hui, AU - Matsumoto,Taro, AU - Kobayashi,Naohiko, AU - Suzuki,Ryo, AU - Tahira,Yoshiko, AU - Ueno,Takahiro, AU - Matsumoto,Koichi, PY - 2007/12/20/pubmed PY - 2008/3/14/medline PY - 2007/12/20/entrez SP - 72 EP - 7 JF - American journal of hypertension JO - Am J Hypertens VL - 21 IS - 1 N2 - 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. SN - 0895-7061 UR - https://www.unboundmedicine.com/medline/citation/18091747/Effects_of_an_ARB_on_endothelial_progenitor_cell_function_and_cardiovascular_oxidation_in_hypertension_ L2 - https://academic.oup.com/ajh/article-lookup/doi/10.1038/ajh.2007.5 DB - PRIME DP - Unbound Medicine ER -