N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster
Autor: | Akira Moriguchi, Koji Yamashita, Toshiji Iwasaka, Yuzo Akita, Toru Okazaki, Seiji Matsuhisa, Hajime Otani, Daisuke Sato |
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Rok vydání: | 2008 |
Předmět: |
Male
Benzylamines Physiology Clinical Biochemistry Cardiomyopathy Amidines Nitric Oxide Synthase Type II medicine.disease_cause Biochemistry Ventricular Function Left Acetylcysteine Phosphatidylinositol 3-Kinases Cricetinae Medicine Drug Interactions Enzyme Inhibitors Phosphorylation General Environmental Science Ventricular Remodeling Heart Free Radical Scavengers Organ Size Losartan NG-Nitroarginine Methyl Ester Cardiomyopathies medicine.drug medicine.medical_specialty Nitric Oxide Synthase Type III Heart Ventricles Hamster Internal medicine Animals Ventricular remodeling Molecular Biology business.industry Myocardium Cell Biology medicine.disease Angiotensin II Fibrosis Oxidative Stress Endocrinology Heart failure General Earth and Planetary Sciences business Angiotensin II Type 1 Receptor Blockers Proto-Oncogene Proteins c-akt Oxidative stress |
Zdroj: | Antioxidantsredox signaling. 10(12) |
ISSN: | 1557-7716 |
Popis: | Oxidative stress mediated by activation of angiotensin II type-1 receptor (AT(1)R) plays a crucial role in the progression of heart failure. We investigated the effect of N-acetylcysteine (NAC) and an AT(1)R blocker on oxidative stress and left ventricular (LV) remodeling in BIO14.6 cardiomyopathy hamsters. The cardiomyopathy hamsters were treated with NAC or the AT(1)R blocker losartan for 20 weeks. Although NAC and losartan inhibited oxidative stress and upregulation of iNOS in the cardiomyopathy hamster heart, only losartan inhibited LV chamber dilation, myocardial fibrosis, and LV dysfunction in the cardiomyopathy hamster. Co-treatment with NAC abolished the protective effect of losartan against LV remodeling associated with inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt and eNOS activation. An iNOS inhibitor 1400W or a nonselective NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) exacerbated LV remodeling in the cardiomyopathy hamster. However, L-NAME but not 1400W abrogated losartan-mediated inhibition of LV remodeling. These results suggest that redox-sensitive upregulation of iNOS plays a crucial role in preventing LV remodeling in the BIO14.6 cardiomyopathy hamster. Losartan inhibits LV remodeling by switching the cardioprotective mechanism from iNOS- to eNOS-dependence, but NAC abolishes the protective effect of losartan by inhibiting redox-sensitive activation of PI3K/Akt and eNOS in the cardiomyopathy hamster. |
Databáze: | OpenAIRE |
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