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Inhibition of Peroxynitrite Formation Attenuates MI/R Injury in Adiponectin Deficient Mice
Author(s) -
Tao Ling,
Jiao Xiangying,
Yuan Yuexing,
Christopher Theodore,
Lopez Bernard,
Chan Lawrence,
Goldstein Barry,
Ma Xin L
Publication year - 2007
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.21.6.a1374-a
Subject(s) - peroxynitrite , nitrotyrosine , chemistry , adiponectin , oxidative stress , apoptosis , medicine , endocrinology , peroxynitrous acid , pharmacology , reperfusion injury , biochemistry , ischemia , superoxide , enzyme , nitric oxide synthase , insulin , insulin resistance
Myocardial peroxynitrite (ONOO−) production is increased and ischemia/reperfusion (I/R) injury is potentiated in adiponectin knockout (Adp−/−) mice, suggesting that adiponectin may exert its protective effects by inhibiting the production of ONOO−. The present study was designed to obtain direct evidence to support a causative link between ONOO− overproduction and increased MI/R injury in Adp−/− mice. Male adult wild type (WT) or Adp−/− mice were subjected to MI/R (30 min/3 hours). Myocardial ONOO− formation (nitrotyrosine content) and myocardial apoptosis was determined. Consistent with our previous findings, ONOO− production and capsase‐3 activation were significantly higher in the Adp−/− heart than the WT heart (P<0.01). Treatment with 1400W (2 mg/kg), a selective iNOS inhibitor, or M40401 (0.25 mg/kg), an ONOO− scavenger, 10 minutes before reperfusion blocked nitrotyrosine overproduction in Adi−/− mice, indicating that these treatments effectively reduced ONOO− content in I/R cardiac tissue. Most interestingly, these treatments also markedly attenuated myocardial apoptosis in Adi−/− animas as determined by caspase 3 activity (4.8±0.7 and 5.20±0.7 vs. 9.1±0.6 nmol/h/mg protein in vehicle‐treated mice, P<0.01). These results provided clear evidence that increased oxidative and nitrative stress in Adi−/− mice plays a causative role in the accelerated MI/R injury observed in these animals.