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l ‐Arginine Attenuates Cardiac Dysfunction, But Further Down‐Regulates α‐Myosin Heavy Chain Expression in Isoproterenol‐Induced Cardiomyopathy
Author(s) -
Kralova Eva,
Doka Gabriel,
Pivackova Lenka,
Srankova Jasna,
Kuracinova Kristina,
Janega Pavol,
Babal Pavel,
Klimas Jan,
Krenek Peter
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12405
Subject(s) - medicine , nitric oxide , endocrinology , nitric oxide synthase , muscle hypertrophy , myh7 , fibrosis , brain natriuretic peptide , myh6 , cardiac function curve , atrial natriuretic peptide , myosin , cardiology , heart failure , chemistry , myosin light chain kinase , biochemistry
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 MYH 6 and unaltered expression of pathological MYH 7. 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 MYH 7 expression and a down‐regulation of MYH 6 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 MYH 7 which may compensate for the marked down‐regulation of the major MYH 6 isoform.