TY - JOUR
T1 - eNOS is required for acute in vivo ischemic preconditioning of the heart
T2 - Effects of ischemic duration and sex
AU - Talukder, M. A Hassan
AU - Yang, Fuchun
AU - Shimokawa, Hiroaki
AU - Zweier, Jay L.
PY - 2010/8
Y1 - 2010/8
N2 - Ischemic preconditioning (IPC) is a powerful phenomenon that provides potent cardioprotection in mammalian hearts; however, the role of endothelial nitric oxide (NO) synthase (eNOS)-mediated NO in this process remains highly controversial. Questions also remain regarding this pathway as a function of sex and ischemic duration. Therefore, we performed extensive experiments in wild-type (WT) and eNOS knockout (eNOS-/-) mice to evaluate whether the infarct-limiting effect of IPC depends on eNOS, ischemic periods, and sex. Classical IPC was induced by three cycles of 5 min of regional coronary ischemia separated by 5 min of reperfusion and was followed by 30 or 60 min of sustained ischemia and 24 h of reperfusion. The control ischemia-reperfusion protocol had 30 or 60 min of ischemia followed by 24 h of reperfusion. Protection was evaluated by measuring the myocardial infarct size as a percentage of the area at risk. The major findings were that regardless of sex, WT mice exhibited robust IPC with significantly smaller myocardial infarction, whereas eNOS -/- mice did not. IPC-induced cardiac protection was absent in eNOS-/- mice of both Jackson and Harvard origin. In general, female WT mice had smaller infarctions compared with male WT mice. Although prolonged ischemia caused significantly larger infarctions in WT mice of both sexes, they were consistently protected by IPC. Importantly, prolonged myocardial ischemia was associated with increased mortality in eNOS-/- mice, and the survival rate was higher in female eNOS-/- mice compared with male eNOS-/- mice. In conclusion, IPC protects WT mice against in vivo myocardial ischemia-reperfusion injury regardless of sex and ischemic duration, but the deletion of eNOS abolishes the cardioprotective effect of classical IPC.
AB - Ischemic preconditioning (IPC) is a powerful phenomenon that provides potent cardioprotection in mammalian hearts; however, the role of endothelial nitric oxide (NO) synthase (eNOS)-mediated NO in this process remains highly controversial. Questions also remain regarding this pathway as a function of sex and ischemic duration. Therefore, we performed extensive experiments in wild-type (WT) and eNOS knockout (eNOS-/-) mice to evaluate whether the infarct-limiting effect of IPC depends on eNOS, ischemic periods, and sex. Classical IPC was induced by three cycles of 5 min of regional coronary ischemia separated by 5 min of reperfusion and was followed by 30 or 60 min of sustained ischemia and 24 h of reperfusion. The control ischemia-reperfusion protocol had 30 or 60 min of ischemia followed by 24 h of reperfusion. Protection was evaluated by measuring the myocardial infarct size as a percentage of the area at risk. The major findings were that regardless of sex, WT mice exhibited robust IPC with significantly smaller myocardial infarction, whereas eNOS -/- mice did not. IPC-induced cardiac protection was absent in eNOS-/- mice of both Jackson and Harvard origin. In general, female WT mice had smaller infarctions compared with male WT mice. Although prolonged ischemia caused significantly larger infarctions in WT mice of both sexes, they were consistently protected by IPC. Importantly, prolonged myocardial ischemia was associated with increased mortality in eNOS-/- mice, and the survival rate was higher in female eNOS-/- mice compared with male eNOS-/- mice. In conclusion, IPC protects WT mice against in vivo myocardial ischemia-reperfusion injury regardless of sex and ischemic duration, but the deletion of eNOS abolishes the cardioprotective effect of classical IPC.
KW - Cardioprotection
KW - Endothelial nitric oxide synthase
KW - Gender
KW - Ischemic periods
KW - Mortality
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U2 - 10.1152/ajpheart.00384.2010
DO - 10.1152/ajpheart.00384.2010
M3 - Article
C2 - 20525875
AN - SCOPUS:77955453735
SN - 0363-6135
VL - 299
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2
ER -