Angiotensin II Receptor Blocker Reduces Oxidative Stress and Attenuates Hypoxia-Induced Left Ventricular Remodeling in Apolipoprotein E-Knockout Mice
Autor: | Yoshikatsu Okada, Naoko Tazawa, Yasuo Matsumura, Koichi Sohmiya, Tetsuya Hayashi, Chika Yamashita, Chol-Jun Kwak, Yasushi Kitaura, Daisuke Nakano, Tatsuhiko Mori |
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Rok vydání: | 2007 |
Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Angiotensin receptor Apolipoprotein B Physiology Heart Ventricles Tetrazoles Matrix Metalloproteinase Inhibitors Biology medicine.disease_cause Muscle hypertrophy Mice Apolipoproteins E Superoxides Internal medicine Internal Medicine medicine Animals Myocytes Cardiac Hypoxia Ventricular remodeling Mice Knockout Aldehydes Ventricular Remodeling Imidazoles NF-kappa B NADPH Oxidases Hypoxia (medical) medicine.disease Oxidative Stress Endocrinology Matrix Metalloproteinase 9 biology.protein Hypertrophy Left Ventricular medicine.symptom Cardiology and Cardiovascular Medicine Olmesartan Angiotensin II Type 1 Receptor Blockers Oxidative stress medicine.drug |
Zdroj: | Hypertension Research. 30:1219-1230 |
ISSN: | 1348-4214 0916-9636 |
Popis: | 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. |
Databáze: | OpenAIRE |
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