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Glutathione Reverses Peroxynitrite-mediated Deleterious Effects of Nitroglycerin on Ischemic Rat Hearts
- Source :
- Journal of Cardiovascular Pharmacology. 47:405-412
- Publication Year :
- 2006
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2006.
-
Abstract
- 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.
- Subjects :
- Male
Cardiac function curve
Necrosis
Myocardial Ischemia
Ischemia
Apoptosis
Myocardial Reperfusion Injury
Pharmacology
Rats, Sprague-Dawley
Nitroglycerin
chemistry.chemical_compound
Peroxynitrous Acid
Lactate dehydrogenase
medicine
Animals
Myocytes, Cardiac
business.industry
Nitrotyrosine
Glutathione
medicine.disease
Myocardial Contraction
Rats
chemistry
Anesthesia
Tyrosine
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Reperfusion injury
Peroxynitrite
Subjects
Details
- ISSN :
- 01602446
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Journal of Cardiovascular Pharmacology
- Accession number :
- edsair.doi.dedup.....fc326c421ccf77e798d55cd2517f896c