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Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia-induced left ventricular remodeling in apolipoprotein E-knockout mice.
Hypertens Res. 2007 Dec; 30(12):1219-30.HR

Abstract

Elevated superoxide formation in cardiac extracts of apolipoprotein E-knockout (apoE-KO) mice has been reported. In addition, we previously reported that hypoxia increased oxidative stress in the aortas of apoE-KO mice, although we did not examine the effect of hypoxia on the heart. The aim of this study was to investigate the effect of chronic hypoxia on the left ventricular (LV) remodeling in apoE-KO mice treated with or without an angiotensin II receptor blocker. Male apoE-KO mice (n=83) and wild-type mice (n=34) at 15 weeks of age were kept under hypoxic conditions (oxygen, 10.0+/-0.5%) and treated with olmesartan (3 mg/kg/day) or vehicle for 3 weeks. Although LV pressure was not changed, hypoxia caused hypertrophy of cardiomyocytes and increased interstitial fibrosis in the LV myocardium. Furthermore, nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase (MMP)-9 activities were increased in apoE-KO mice exposed to chronic hypoxia. Olmesartan effectively suppressed the 4-hydroxy-2-nonenal protein expression and NF-kappaB and MMP-9 activities, and preserved the fine structure of the LV myocardium without affecting the LV pressure. In conclusion, olmesartan reduced oxidative stress, and attenuated the hypoxia-induced LV remodeling, in part through the inhibition of NF-kappaB and MMP-9 activities, in apoE-KO mice.

Authors+Show Affiliations

Osaka University of Pharmaceutical Sciences, Takatsuki, 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 availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18344628

Citation

Yamashita, Chika, et al. "Angiotensin II Receptor Blocker Reduces Oxidative Stress and Attenuates Hypoxia-induced Left Ventricular Remodeling in Apolipoprotein E-knockout Mice." Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 30, no. 12, 2007, pp. 1219-30.
Yamashita C, Hayashi T, Mori T, et al. Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia-induced left ventricular remodeling in apolipoprotein E-knockout mice. Hypertens Res. 2007;30(12):1219-30.
Yamashita, C., Hayashi, T., Mori, T., Tazawa, N., Kwak, C. J., Nakano, D., Sohmiya, K., Okada, Y., Kitaura, Y., & Matsumura, Y. (2007). Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia-induced left ventricular remodeling in apolipoprotein E-knockout mice. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 30(12), 1219-30. https://doi.org/10.1291/hypres.30.1219
Yamashita C, et al. Angiotensin II Receptor Blocker Reduces Oxidative Stress and Attenuates Hypoxia-induced Left Ventricular Remodeling in Apolipoprotein E-knockout Mice. Hypertens Res. 2007;30(12):1219-30. PubMed PMID: 18344628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia-induced left ventricular remodeling in apolipoprotein E-knockout mice. AU - Yamashita,Chika, AU - Hayashi,Tetsuya, AU - Mori,Tatsuhiko, AU - Tazawa,Naoko, AU - Kwak,Chol-Jun, AU - Nakano,Daisuke, AU - Sohmiya,Koichi, AU - Okada,Yoshikatsu, AU - Kitaura,Yasushi, AU - Matsumura,Yasuo, PY - 2008/3/18/pubmed PY - 2008/4/25/medline PY - 2008/3/18/entrez SP - 1219 EP - 30 JF - Hypertension research : official journal of the Japanese Society of Hypertension JO - Hypertens Res VL - 30 IS - 12 N2 - Elevated superoxide formation in cardiac extracts of apolipoprotein E-knockout (apoE-KO) mice has been reported. In addition, we previously reported that hypoxia increased oxidative stress in the aortas of apoE-KO mice, although we did not examine the effect of hypoxia on the heart. The aim of this study was to investigate the effect of chronic hypoxia on the left ventricular (LV) remodeling in apoE-KO mice treated with or without an angiotensin II receptor blocker. Male apoE-KO mice (n=83) and wild-type mice (n=34) at 15 weeks of age were kept under hypoxic conditions (oxygen, 10.0+/-0.5%) and treated with olmesartan (3 mg/kg/day) or vehicle for 3 weeks. Although LV pressure was not changed, hypoxia caused hypertrophy of cardiomyocytes and increased interstitial fibrosis in the LV myocardium. Furthermore, nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase (MMP)-9 activities were increased in apoE-KO mice exposed to chronic hypoxia. Olmesartan effectively suppressed the 4-hydroxy-2-nonenal protein expression and NF-kappaB and MMP-9 activities, and preserved the fine structure of the LV myocardium without affecting the LV pressure. In conclusion, olmesartan reduced oxidative stress, and attenuated the hypoxia-induced LV remodeling, in part through the inhibition of NF-kappaB and MMP-9 activities, in apoE-KO mice. SN - 0916-9636 UR - https://www.unboundmedicine.com/medline/citation/18344628/Angiotensin_II_receptor_blocker_reduces_oxidative_stress_and_attenuates_hypoxia_induced_left_ventricular_remodeling_in_apolipoprotein_E_knockout_mice_ DB - PRIME DP - Unbound Medicine ER -