BACKGROUND: The role of endothelial nitric oxide synthase (eNOS) in isoflurane postconditioning (IsoPC)-elicited cardioprotection is poorly understood. The authors addressed this issue using eNOS mice. METHODS: In vivo or Langendorff-perfused mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in the presence and absence of postconditioning produced with isoflurane 5 min before and 3 min after reperfusion. Ca+-induced mitochondrial permeability transition (MPT) pore opening was assessed in isolated mitochondria. Echocardiography was used to evaluate ventricular function. RESULTS: Postconditioning with 0.5, 1.0, and 1.5 minimum alveolar concentrations of isoflurane decreased infarct size from 56 +/- 10% (n = 10) in control to 48 +/- 10%, 41 +/- 8% (n = 8, P < 0.05), and 38 +/- 10% (n = 8, P < 0.05), respectively, and improved cardiac function in wild-type mice. Improvement in cardiac function by IsoPC was blocked by N-nitro-L-arginine methyl ester (a nonselective nitric oxide synthase inhibitor) administered either before ischemia or at the onset of reperfusion. Mitochondria isolated from postconditioned hearts required significantly higher in vitro Ca+ loading than did controls (78 +/- 29 microm vs. 40 +/- 25 microm CaCl2 per milligram of protein, n = 10, P < 0.05) to open the MPT pore. Hearts from eNOS mice displayed no marked differences in infarct size, cardiac function, and sensitivity of MPT pore to Ca+, compared with wild-type hearts. However, IsoPC failed to alter infarct size, cardiac function, or the amount of Ca+ necessary to open the MPT pore in mitochondria isolated from the eNOS hearts compared with control hearts. CONCLUSIONS: IsoPC protects mouse hearts from reperfusion injury by preventing MPT pore opening in an eNOS-dependent manner. Nitric oxide functions as both a trigger and a mediator of cardioprotection produced by IsoPC.
BACKGROUND: The role of endothelial nitric oxide synthase (eNOS) in isoflurane postconditioning (IsoPC)-elicited cardioprotection is poorly understood. The authors addressed this issue using eNOSmice. METHODS: In vivo or Langendorff-perfused mouse hearts underwent 30 min of ischemia followed by 2 h of reperfusion in the presence and absence of postconditioning produced with isoflurane 5 min before and 3 min after reperfusion. Ca+-induced mitochondrial permeability transition (MPT) pore opening was assessed in isolated mitochondria. Echocardiography was used to evaluate ventricular function. RESULTS: Postconditioning with 0.5, 1.0, and 1.5 minimum alveolar concentrations of isoflurane decreased infarct size from 56 +/- 10% (n = 10) in control to 48 +/- 10%, 41 +/- 8% (n = 8, P < 0.05), and 38 +/- 10% (n = 8, P < 0.05), respectively, and improved cardiac function in wild-type mice. Improvement in cardiac function by IsoPC was blocked by N-nitro-L-arginine methyl ester (a nonselective nitric oxide synthase inhibitor) administered either before ischemia or at the onset of reperfusion. Mitochondria isolated from postconditioned hearts required significantly higher in vitro Ca+ loading than did controls (78 +/- 29 microm vs. 40 +/- 25 microm CaCl2 per milligram of protein, n = 10, P < 0.05) to open the MPT pore. Hearts from eNOSmice displayed no marked differences in infarct size, cardiac function, and sensitivity of MPT pore to Ca+, compared with wild-type hearts. However, IsoPC failed to alter infarct size, cardiac function, or the amount of Ca+ necessary to open the MPT pore in mitochondria isolated from the eNOS hearts compared with control hearts. CONCLUSIONS: IsoPC protects mouse hearts from reperfusion injury by preventing MPT pore opening in an eNOS-dependent manner. Nitric oxide functions as both a trigger and a mediator of cardioprotection produced by IsoPC.
Authors: P S Brookes; E P Salinas; K Darley-Usmar; J P Eiserich; B A Freeman; V M Darley-Usmar; P G Anderson Journal: J Biol Chem Date: 2000-07-07 Impact factor: 5.157
Authors: Hartmut Ruetten; Stefanie Dimmeler; Doris Gehring; Christian Ihling; Andreas M Zeiher Journal: Cardiovasc Res Date: 2005-02-24 Impact factor: 10.787
Authors: Pierre Sicard; Sebastien Jacquet; Koichi S Kobayashi; Richard A Flavell; Michael S Marber Journal: Cardiovasc Res Date: 2009-02-12 Impact factor: 10.787
Authors: Zhi-Dong Ge; Irina A Ionova; Nikolina Vladic; Danijel Pravdic; Naoyuki Hirata; Jeannette Vásquez-Vivar; Phillip F Pratt; David C Warltier; Galen M Pieper; Judy R Kersten Journal: Cardiovasc Res Date: 2011-03-21 Impact factor: 10.787
Authors: Thorsten M Leucker; Martin Bienengraeber; Maria Muravyeva; Ines Baotic; Dorothee Weihrauch; Anna K Brzezinska; David C Warltier; Judy R Kersten; Phillip F Pratt Journal: J Mol Cell Cardiol Date: 2011-07-21 Impact factor: 5.000
Authors: Nikolina Vladic; Zhi-Dong Ge; Thorsten Leucker; Anna K Brzezinska; Jian-Hai Du; Yang Shi; David C Warltier; Phillip F Pratt; Judy R Kersten Journal: Am J Physiol Heart Circ Physiol Date: 2011-09-09 Impact factor: 4.733
Authors: Shigang Qiao; Jessica M Olson; Mark Paterson; Yasheng Yan; Ivan Zaja; Yanan Liu; Matthias L Riess; Judy R Kersten; Mingyu Liang; David C Warltier; Zeljko J Bosnjak; Zhi-Dong Ge Journal: Anesthesiology Date: 2015-10 Impact factor: 7.892
Authors: Muhammad Z Afzal; Melanie Reiter; Courtney Gastonguay; Jered V McGivern; Xuan Guan; Zhi-Dong Ge; David L Mack; Martin K Childers; Allison D Ebert; Jennifer L Strande Journal: J Cardiovasc Pharmacol Ther Date: 2016-03-02 Impact factor: 2.457