TY - JOUR
T1 - Prevention of postischemic myocardial reperfusion injury by the combined treatment of NCX-4016 and Tempol
AU - Kutala, Vijay Kumar
AU - Khan, Mahmood
AU - Mandal, Rajarsi
AU - Potaraju, Vandana
AU - Colantuono, Giuseppe
AU - Kumbala, Damodar
AU - Kuppusamy, Periannan
PY - 2006/9
Y1 - 2006/9
N2 - Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion (I/R) injury. However, the concomitant production of superoxide and other reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO and hence compromise the beneficial effects. The objective of this study was to investigate the protective effect of the coadministration of NCX-4016 [2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester] (an NO donor) with antioxidants Tempol, superoxide dismutase (SOD), or urate on I/R injury. Isolated rat hearts, perfused with Krebs-Henseleit buffer, were subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. Before the induction of ischemia, the hearts were infused for 1 minute with NCX-4016 (100 μM) either alone or in combination with Tempol (100 μM), SOD (200 U/mL), or urate (100 μM). Hearts pretreated with NCX-4016 showed a significantly enhanced recovery of function and decreased infarct size and LDH/CK release compared with the controls. However, treatment of hearts with NCX-4016 + Tempol, SOD, or urate showed a significantly enhanced recovery of heart function compared with NCX-4016 alone. The treatment of hearts with NCX-4016 + Tempol showed significantly enhanced NO generation and decreased ROS and dityrosine (a marker of peroxynitrite) formation. In conclusion, NCX-4016 in combination with Tempol demonstrated significant cardioprotection and, thus, may offer a novel therapeutic strategy to prevent I/R-mediated myocardial injury.
AB - Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion (I/R) injury. However, the concomitant production of superoxide and other reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO and hence compromise the beneficial effects. The objective of this study was to investigate the protective effect of the coadministration of NCX-4016 [2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester] (an NO donor) with antioxidants Tempol, superoxide dismutase (SOD), or urate on I/R injury. Isolated rat hearts, perfused with Krebs-Henseleit buffer, were subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. Before the induction of ischemia, the hearts were infused for 1 minute with NCX-4016 (100 μM) either alone or in combination with Tempol (100 μM), SOD (200 U/mL), or urate (100 μM). Hearts pretreated with NCX-4016 showed a significantly enhanced recovery of function and decreased infarct size and LDH/CK release compared with the controls. However, treatment of hearts with NCX-4016 + Tempol, SOD, or urate showed a significantly enhanced recovery of heart function compared with NCX-4016 alone. The treatment of hearts with NCX-4016 + Tempol showed significantly enhanced NO generation and decreased ROS and dityrosine (a marker of peroxynitrite) formation. In conclusion, NCX-4016 in combination with Tempol demonstrated significant cardioprotection and, thus, may offer a novel therapeutic strategy to prevent I/R-mediated myocardial injury.
KW - Antioxidant
KW - Ischemia-reperfusion injury
KW - NCX-4016
KW - Nitric oxide
KW - Nitro-aspirin
KW - Oxidative stress
KW - Tempol
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U2 - 10.1097/01.fjc.0000242050.16790.65
DO - 10.1097/01.fjc.0000242050.16790.65
M3 - Article
C2 - 17031260
AN - SCOPUS:33749846221
SN - 0160-2446
VL - 48
SP - 79
EP - 87
JO - Journal of cardiovascular pharmacology
JF - Journal of cardiovascular pharmacology
IS - 3
ER -