eNOS is required for acute in vivo ischemic preconditioning of the heart: effects of ischemic duration and sex
- 1 August 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 299 (2), H437-H445
- https://doi.org/10.1152/ajpheart.00384.2010
Abstract
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.Keywords
This publication has 64 references indexed in Scilit:
- Cardiac Myocyte–Specific Expression of Inducible Nitric Oxide Synthase Protects Against Ischemia/Reperfusion Injury by Preventing Mitochondrial Permeability TransitionCirculation, 2008
- Endothelial nitric oxide synthase is not necessary for the early phase of ischemic preconditioning in the mouseJournal of Molecular and Cellular Cardiology, 2008
- Impact of Ischemia and Reperfusion Times on Myocardial Infarct Size in Mice In VivoExperimental Biology and Medicine, 2008
- Cardioprotection Afforded by Inducible Nitric Oxide Synthase Gene Therapy Is Mediated by Cyclooxygenase-2 via a Nuclear Factor-κB–Dependent PathwayCirculation, 2007
- Expression of SERCA isoform with faster Ca2+ transport properties improves postischemic cardiac function and Ca2+ handling and decreases myocardial infarctionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Endothelial Nitric Oxide Synthase Plays an Obligatory Role in the Late Phase of Ischemic Preconditioning by Activating the Protein Kinase Cε–p44/42 Mitogen-Activated Protein Kinase–pSer-Signal Transducers and Activators of Transcription1/3 PathwayCirculation, 2007
- Endothelial nitric oxide synthase (NOS3) knockout decreases NOS2 induction, limiting hyperoxygenation and conferring protection in the postischemic heartAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Cytochrome and arachidonic acid metabolites: Role in myocardial ischemia/reperfusion injury revisitedCardiovascular Research, 2005
- Nitric oxide in myocardial ischemia/reperfusion injuryCardiovascular Research, 2004
- Endothelial Nitric Oxide Gene Knockout MiceHypertension, 1999