Signal transduction in myocardial ischaemia and reperfusion

Amanda Lochner, Erna Tromp, R Mouton

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Recent studies in the non-ischaemic myocardium indicated that drugs stimulating cAMP formation inhibit alpha 1-mediated inositol phosphate generation, while alpha 1-adrenergic stimulation lowered tissue cAMP levels, implicating cross-talk between alpha 1- and beta-adrenergic signalling pathways in normal physiological conditions. Massive amounts of endogenous catecholamines, predominantly noradrenaline, are released during myocardial ischaemia and reperfusion, causing stimulation of both alpha 1- and beta-adrenergic receptors which, in turn, may contribute to intracellular Ca2+ overload and subsequent cell damage. Since no information is available regarding cross-talk in pathophysiological conditions, the aim of this study was to evaluate the interactions between alpha 1- and beta-adrenergic signalling pathways during different periods of ischaemia and reperfusion. Isolated rat hearts were perfused retrogradely for 30 min before being subjected to (i) 5-25 min global ischaemia and (ii) 1-5 min of reperfusion after 20 min global ischaemia. Drugs (prazosin, 10(-7) M; propranolol, 10(-6) M; phenylephrine 3 x 10(-5) M; isoproterenol 10(-9) M) were added 10 min before the onset of ischaemia and were present during reperfusion. Increasing periods of ischaemia caused an immediate rise and progressive lowering in tissue cAMP and Ins(1,4,5)P3 levels respectively. In contrast, reperfusion caused an elevation in Ins(1,4,5)P3 levels and reduced cAMP. Prazosin elevated cAMP levels during both ischaemia and reperfusion, while propranolol had no effects on tissue Ins(1,4,5)P3. The activity of the alpha 1-adrenergic signal transduction pathway appears to have an inhibitory effect on the activity of the beta-adrenergic system during ischaemia and reperfusion.

Original languageEnglish
Pages (from-to)129-36
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume160-161
DOIs
Publication statusPublished - 1 Jul 1996

Keywords

  • Adrenergic alpha-Antagonists/metabolism
  • Adrenergic beta-Antagonists/metabolism
  • Animals
  • Cyclic AMP/metabolism
  • Inositol/metabolism
  • Inositol 1,4,5-Trisphosphate/metabolism
  • Isoproterenol/pharmacology
  • Male
  • Myocardial Ischemia/physiopathology
  • Myocardial Reperfusion Injury/physiopathology
  • Phenylephrine/pharmacology
  • Prazosin/pharmacology
  • Propranolol/pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha/metabolism
  • Receptors, Adrenergic, beta/metabolism
  • Signal Transduction/physiology

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