caa a22 4500 475833538 CHVBK 20180406123847.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1023/A:1007847111368 doi (NATIONALLICENCE)springer-10.1023/A:1007847111368 SB 203580, a Mitogen-Activated Protein Kinase Inhibitor, Abolishes Resistance to Myocardial Infarction Induced by Heat Stress [Elektronische Daten] [Marie Joyeux, Ahcène Boumendjel, Richard Carroll, Christophe Ribuot, Diane Godin-Ribuot, Derek Yellon] Heat stress (HS) is known to confer protection against ischemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the mechanisms involved in this cardioprotection are yet to be elucidated. Mitogen-activated protein (MAP) kinase cascades have been demonstrated to be involved in cellular response to different stresses. In particular, p38 MAP kinase is known to be activated by HS. Therefore, we investigated the implication of this kinase in HS-induced resistance to myocardial infarction, in the isolated rat heart model, using SB 203580 (SB) to selectively inhibit p38 MAP kinase. Rats were treated with SB (2.83 mg/kg, i.p.) or vehicle (1% DMSO in saline, i.p.) before they were either heat stressed (42°C for 15 minutes) or sham anesthetized. Their hearts were isolated 24 hours later, retrogradely perfused, and subjected to a 35-minute occlusion of the left coronary artery followed by 120 minutes of reperfusion. The infarct-to-risk ratio was significantly reduced in HS (16.9 ± 2.0%) compared with sham (41.6 ± 2.5%) hearts. This reduction in infarct size was abolished in the SB 203580-treated group (37.8 ± 1.9% in HS + SB vs. 42.0 ± 1.9% in sham + SB). Risk zones were similar between experimental groups. Western blot analysis of the myocardial HSP72 showed an HS-induced increase of this protein, which was not modified by the p38 MAP kinase inhibitor, SB 203580. We conclude that activation of p38 MAP kinase appears to play a role in the functional cardioprotection associated with the heat stress response, which seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the p38 MAP kinase and heat stress proteins in this adaptative response. Kluwer Academic Publishers, 2000 heat stress nationallicence infarct size nationallicence mitogen-activated protein kinase nationallicence SB 203580 nationallicence heat stress protein nationallicence Joyeux Marie Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut Boumendjel Ahcène Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut Carroll Richard The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, UK aut Ribuot Christophe Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut Godin-Ribuot Diane Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut Yellon Derek The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, UK aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/3(2000-03-01), 337-343 0920-3206 14:3<337 2000 14 10557 https://doi.org/10.1023/A:1007847111368 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007847111368 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Joyeux Marie Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut NATIONALLICENCE 700 1- Boumendjel Ahcène Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut NATIONALLICENCE 700 1- Carroll Richard The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, UK aut NATIONALLICENCE 700 1- Ribuot Christophe Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut NATIONALLICENCE 700 1- Godin-Ribuot Diane Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, U.F.R. de Pharmacie, Grenoble, France aut NATIONALLICENCE 700 1- Yellon Derek The Hatter Institute for Cardiovascular Studies, University College London Hospitals & Medical School, London, UK aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/3(2000-03-01), 337-343 0920-3206 14:3<337 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer