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
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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