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Signal transduction in myocardial ischaemia and reperfusion

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Abstract

Recent studies in the non-ischaemic myocardium indicated that drugs stimulating cAMP formation inhibit α1-mediated inositol phosphate generation, while α1-adrenergic stimulation lowered tissue CAMP levels, implicating cross-talk between α1,- and β-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 α1- and β-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 α1- and β-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 × 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 α1-adrenergic signal transduction pathway appears to have an inhibitory effect on the activity of the β-adrenergic system during ischaemia and reperfusion.

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Authors and Affiliations

  1. Department of Medical Physiology and Biochemistry, University of Stellenbosch Faculty of Medicine; MRC Programme for Experimental Biology, 7505, Tygerberg, Republic of South Africa

    A. Lochner, E. Tromp & R. Mouton

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  1. A. Lochner
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  2. E. Tromp
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  3. R. Mouton
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Lochner, A., Tromp, E. & Mouton, R. Signal transduction in myocardial ischaemia and reperfusion. Mol Cell Biochem 160, 129–136 (1996). https://doi.org/10.1007/BF00240042

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