Glutathione reverses peroxynitrite-mediated deleterious effects of nitroglycerin on ischemic rat hearts.
This study examined the potential deleterious effect of high-dose nitroglycerin (NTG) on cardiac function and cellular injury after ischemia (30 min) and reperfusion (120 min) in isolated perfused rat hearts. Low-dose (0.75 microg/h), medium-dose (3.75 microg/h), high-dose (15 microg/h) NTG or high-dose NTG plus glutathione (GSH, 1 mmol/L) was administrated at the time of reperfusion. Administration of high-dose NTG significantly exacerbated cardiac reperfusion injury as evidenced by increased creatine kinase and lactate dehydrogenase activity in coronary effluent, increased cardiomyocyte apoptosis and necrosis, and decreased cardiac function recovery after reperfusion. Compared with the vehicle group, formation of nitrotyrosine, a footprint for peroxynitrite (ONOO) production, was markedly increased in the hearts treated with medium-dose or high-dose NTG. Most interestingly, cotreatment with GSH blocked high-dose NTG-induced ONOO formation and attenuated myocardial ischemia/reperfusion injury. Taken together, our present results demonstrated that administration of high-dose NTG aggravated, rather than attenuated myocardial ischemia/reperfusion injury likely via increasing ONOO formation. Coadministration of GSH may reverse the advert action of high-dose NTG.
Fan
Qian
Q
Heart Center, Beijing Chaoyang Hospital-Affiliate of Capital University of Medical Sciences, PR China.
Yang
Xin Chun
XC
Cao
Xue Bin
XB
Wang
Shu Yan
SY
Yang
Shu Ling
SL
Liu
Xiu Lan
XL
Gao
Feng
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D005996:Nitroglycerin / Q000633:toxicity*; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D005996:Nitroglycerin; D005978:Glutathione