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Title of Journal: Apoptosis

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Abbravation: Apoptosis

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Kluwer Academic Publishers

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DOI

10.1016/0378-4274(82)90195-3

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ISSN

1573-675X

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Nitrate tolerance aggravates postischemic myocardi

Authors: Q Fan F Gao L Zhang T A Christopher B L Lopez X L Ma
Publish Date: 2005/10/03
Volume: 10, Issue: 6, Pages: 1235-1242
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Abstract

Objectives This study examined the effects of nitrate tolerance NT on myocardial ischemia reperfusion MI/R injury and elucidated the potential mechanisms involved Furthermore the effects of GSH on postischemic myocardial apoptosis in NT rats were investigatedMethods and results Male Sprague–Dawley rats were randomized to receive nitroglycerin 60 μg/kg/h or saline for 12 h followed by 40 min of MI and 4 h of reperfusion Myocardial apoptosis infarct size nitrotyrosine formation plasma CK and LDH activity and cardiac function were determined MI/R resulted in significant apoptotic cell death which was further increased in animals with NT In addition NT further increased plasma CK and LDH activity enlarged infarct size and impaired cardiac functional recovery after ischemia Myocardial nitrotyrosine a footprint for cytotoxic reactive nitrogen species formation was further enhanced in the NT heart after MI/R Treatment of NT animals with exogenous GSH inhibited nitrotyrosine formation reduced apoptosis decreased infarct size and improved cardiac functional recoveryConclusion Our results demonstrate that nitrate tolerance markedly enhances MI/R injury and that increased peroxynitrite formation likely plays a role in this pathologic process In addition our results suggest that GSH could decrease peroxynitrite formation and reduce MI/R injury in nitrate tolerant hearts

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