Pharmacological manipulation of Ins(1,4,5)P3 signaling mimics preconditioning in rabbit heart

Anne Gysembergh, Stéphanie Lemaire, Christophe Piot, Catherine Sportouch, Sylvain Richard, Robert A. Kloner, Karin Przyklenk

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Recent evidence revealed biphasic alterations in myocardial concentrations of the second messenger inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] with ischemic preconditioning (PC), i.e., increase during brief PC ischemia and decrease early during sustained test occlusion. Our aim was to determine whether an agonist and an antagonist of Ins(1,4,5)P3 signaling {D-myo-inositol-1,4,5-trisphosphate hexasodium salt [D-myo- Ins(1,4,5)P3] and 2-aminoethoxydiphenyl borate (2-APB), respectively}, given such that they mimic this biphasic profile, would mimic infarct size reduction with PC. To test this concept, isolated, buffer-perfused rabbit hearts received no intervention (control), ischemic PC, D-myo-Ins(1,4,5)P3, D-myo-Ins(1,4,5)P3 + PC, 2-APB, or 2-APB + PC. All hearts then underwent 30- min coronary occlusion and 2 h reflow, and infarct size was delineated by tetrazolium staining. In addition, the effects of D-myo-Ins(1,4,5)P3 and 2- APB on Ins(1,4,5)P3 signaling were evaluated in isolated fura 2-loaded rat cardiomyocytes. Mean infarct size was reduced with PC and in all D-myo- Ins(1,4,5)P3- and 2-APB-treated groups versus control (59 and 42-55%, respectively, vs. 80% of myocardium at risk, P < 0.05). Thus pharmacological manipulation of Ins(1,4,5)P3 signaling mimics the cardioprotection achieved with ischemic PC in rabbit heart.

Original languageEnglish
Pages (from-to)H2458-H2469
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number6 46-6
DOIs
StatePublished - Dec 1999

Keywords

  • 2- aminoethoxydiphenyl borate
  • Calcium
  • Myocardial infarction
  • Myocardial ischemia
  • Signal transduction

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