Premium
Increased Superoxide Production in mdx Heart, Diminished Regulation of Mitochondrial Function by Nitric Oxide.
Author(s) -
Serpillon Sabrina,
Adler Alexandra,
Higashimori Takamasa,
Huang Harer,
Messina Eric,
Hintze Thomas H
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1180-c
Subject(s) - mdx mouse , dystrophin , medicine , oxidative stress , duchenne muscular dystrophy , endocrinology , nitric oxide , superoxide , cardiac function curve , cardiomyopathy , chemistry , reactive oxygen species , cardiology , heart failure , biochemistry , enzyme
Dystrophin deficiency is associated with cardiac conduction abnormalities, arrhythmias and cardiomyopathy. Studies in dystrophin deficient mice ( mdx) suggest that oxidative stress may play a role in the development of muscle necrosis. Our objective was to investigate the interaction between NO and superoxide (O 2 · ) anion production in the development of myocardial dysfunction in mdx mice. 9 mdx and 6 control mice (7 to 11 weeks) were used. Absence of cardiomyopathy in mdx mice was assessed by echocardiograms. Ejection fraction (86±2% in mdx vs 82±4%), Left Ventricular End Diastolic Diameter (2.2±0.1mm in mdx vs 2.3±0.1mm) and Left Ventricular End Diastolic Wall Thickness (0.6mm in mdx vs 0.5mm) were not significantly different. The ability of bradykinin (BK) and SNAP, an NO donor, to decrease the myocardial oxygen consumption (MVO 2 ) was measured in vitro . Both the endogenous and exogenous NO‐dependent MVO 2 reduction were significantly reduced in mdx (p<0.05). Pre‐incubation of tissues with tempol, a O 2 · scavenger, restores the ability of BK and SNAP to control MVO 2 in mdx heart. These results indicate that : 1) O 2 · anion production is increased in mdx heart, reducing NO bioavailability; and 2) the amount of O 2 · is high enough to reduce exogenous NO effect. These data show that oxidative stress occurs as a primary event in mdx heart, before myocardial dysfunction is established. Supported by PO‐1HL43023.