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Basic Research in Cardiology

, Volume 101, Issue 2, pp 180–189 | Cite as

Post–conditioning induced cardioprotection requires signaling through a redox–sensitive mechanism, mitochondrial ATP–sensitive K+ channel and protein kinase C activation

  • C. Penna
  • R. Rastaldo
  • D. Mancardi
  • S. Raimondo
  • S. Cappello
  • D. Gattullo
  • G. Losano
  • P. PagliaroEmail author
ORIGINAL CONTRIBUTION

Abstract

Post–conditioning (Post–C) induced cardioprotection involves activation of guanylyl–cyclase. In the ischemic preconditioning scenario, the downstream targets of cGMP include mitochondrial ATP–sensitive K+ (mKATP) channels and protein kinase C (PKC), which involve reactive oxygen species (ROS) production. This study tests the hypothesis that mKATP, PKC and ROS are also involved in the Post–C protection. Isolated rat hearts underwent 30 min global ischemia (I) and 120 min reperfusion (R) with or without Post–C (i.e., 5 cycles of 10 s R/I immediately after the 30 min ischemia). In 6 groups (3 with and 3 without Post–C) either mKATP channel blocker, 5– hydroxydecanoate (5–HD), or PKC inhibitor, chelerythrine (CHE) or ROS scavenger, N–acetyl–cysteine (NAC), were given during the entire reperfusion (120 min). In other 6 groups (3 with and 3 without Post–C), 5–HD, CHE or NAC were infused for 117 min only starting after 3 min of reperfusion not to interfere with the early effects of Post–C and/or reperfusion. In an additional group NAC was given during Post–C maneuvers (i.e., 3 min only). Myocardial damage was evaluated using nitro–blue tetrazolium staining and lactate dehydrogenase (LDH) release. Post–C attenuated myocardial infarct size (21 ± 3% vs. 64 ± 5% in control; p < 0.01). Such an effect was abolished by 5–HD or CHE given during either the 120 or 117 min of reperfusion as well as by NAC given during the 120 min or the initial 3 min of reperfusion. However, delayed NAC (i.e., 117 min infusion) did not alter the protective effect of Post– C (infarct size 32 ± 5%; p < 0.01 vs. control, NS vs. Post–C). CHE, 5–HD or NAC given in the absence of Post–C did not alter the effects of I/R. Similar results were obtained in terms of LDH release. Our data show that Post–C induced protection involves an early redox–sensitive mechanism as well as a persistent activation of mKATP and PKC, suggesting that the mKATP/ROS/PKC pathway is involved in post–conditioning.

Key words

ischemia/reperfusion mitochondrial KATP channels postconditioning protein kinase C redox signaling 

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Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • C. Penna
    • 1
  • R. Rastaldo
    • 2
  • D. Mancardi
    • 1
  • S. Raimondo
    • 1
  • S. Cappello
    • 2
  • D. Gattullo
    • 1
  • G. Losano
    • 2
  • P. Pagliaro
    • 1
    Email author
  1. 1.Dipartimento di Scienze Cliniche e Biologiche, Università di TorinoOspedale S. Luigi, Regione GonzoleOrbassano (TO)Italy
  2. 2.Sezione di Fisiologia del Dipartimento di NeuroscienzeUniversità di TorinoItaly

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