title: l-Arginine Attenuates Cardiac Dysfunction, But Further Down-Regulates α-Myosin Heavy Chain Expression in Isoproterenol-Induced Cardiomyopathy.
abstract: In view of previously reported increased capacity for nitric oxide production, we suggested that l-arginine (ARG), the nitric oxide synthase (NOS) substrate, supplementation would improve cardiac function in isoproterenol (ISO)-induced heart failure. Male Wistar rats were treated with ISO for 8 days (5 mg/kg/day, i.p.) or vehicle. ARG was given to control (ARG) and ISO-treated (ISO+ARG) rats in water (0.4 g/kg/day). ISO administration was associated with 40% mortality, ventricular hypertrophy, decreased heart rate, left ventricular dysfunction, fibrosis and ECG signs of ischaemia. RT-PCR showed increased mRNA levels of cardiac hypertrophy marker atrial natriuretic peptide, but not BNP, decreased expression of myosin heavy chain isoform MYH6 and unaltered expression of pathological MYH7. ISO increased the protein levels of endothelial nitric oxide synthase, but at the same time it markedly up-regulated mRNA and protein levels of gp91phox, a catalytical subunit of superoxide-producing NADPH oxidase. Fibrosis was markedly increased by ISO. ARG treatment moderately ameliorated left ventricular dysfunction, but was without effect on cardiac hypertrophy and fibrosis. Combination of ISO and ARG led to a decrease in cav-1 expression, a further increase in MYH7 expression and a down-regulation of MYH6 that inversely correlated with gp91phox mRNA levels. Although ARG, at least partially, improved ISO-impaired basal left ventricular systolic function, it failed to reduce cardiac hypertrophy, fibrosis, oxidative stress and mortality. The protection of contractile performance might be related to increased capacity for nitric oxide production and the up-regulation of MYH7 which may compensate for the marked down-regulation of the major MYH6 isoform.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Eva
authors: E
authors: Kralova
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Gabriel
authors: G
authors: Doka
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Lenka
authors: L
authors: Pivackova
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Jasna
authors: J
authors: Srankova
authors: Department of Pathology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Kristina
authors: K
authors: Kuracinova
authors: Department of Pathology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic.|Slovak Academy of Sciences, Institute of Normal and Pathological Anatomy, Bratislava, Slovak Republic.
authors: Pavol
authors: P
authors: Janega
authors: Department of Pathology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Pavel
authors: P
authors: Babal
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Jan
authors: J
authors: Klimas
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic.
authors: Peter
authors: P
authors: Krenek
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D024723:Ventricular Myosins / Q000378:metabolism*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; C000594638:MYH7 protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains; D007545:Isoproterenol