Combination of angiotensin II and l-NG-nitroarginine methyl ester exacerbates mitochondrial dysfunction and oxidative stress to cause heart failure

摘要: Mitochondrial dysfunction has been implicated as a cause of energy deprivation in heart failure (HF). Herein, we tested individual and combined effects two pathogenic factors nonischemic HF, inhibition nitric oxide synthesis [with l-N(G)-nitroarginine methyl ester (l-NAME)] hypertension angiotensin II (AngII)], on myocardial mitochondrial function, oxidative stress, metabolic gene expression. l-NAME AngII were administered individually combination to mice for 5 wk. Although all treatments increased blood pressure reduced cardiac contractile the + group was associated with most severe characterized by edema, hypertrophy, expression Nppa Nppb, decreased Atp2a2 Camk2b. AngII-treated exhibited robust deterioration observed respiratory control ratios subsarcolemmal mitochondria state 3 levels interfibrillar complex I but not substrates. Cardiac myofibrils showed ADP-supported oligomycin-inhibited oxygen consumption. functional impairment accompanied DNA content activities pyruvate dehydrogenase H2O2 production tissue protein carbonyls hearts from groups. Microarray analyses revealed majority changes attributed group. Pathway indicated significant pathways, such phosphorylation, fatty acid metabolism hearts. We conclude that is impaired function stress compared either or alone, resulting HF.