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Ischaemic preconditioning in the rat heart: The role of G-proteins and adrenergic stimulation

  • Part II: Myocytic Adaptation and Myocardial Injury
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Abstract

Since recent findings indicate the involvement of G-proteins in the mechanisms of ischaemic preconditioning (PC), the present study was aimed to investigate the role of adrenergic mechanisms, such as G-proteins and stimulation of adrenergic receptors, in this phenomenon. For this purpose, isolated Langendorff-perfused rat hearts were subjected to regional ischaemia (30 min occlusion of LAD) followed by reperfusion. The effect of PC (a single 5 min occlusion/reperfusion before a long occlusion) on ischaemia- and reperfusion-induced arrhythmias was studied in conjunction with an assessment of G-proteins in the myocardial tissue by means of Western blotting and ADP-ribosylation with bacterial toxins. To follow the link between G-proteins and adrenergic receptors, their stimulation by exogenous norepinephrine (NE) was applied to test whether it can mimic the effect of PC on arrhythmias. Thirty min ischaemia and subsequent reperfusion induced high incidence of ventricular tachycardia (VT) and fibrillation (VF). PC significantly reduced a total number of extrasystoles, incidence of VT and abolished VF. It was, however, insufficient to suppress reperfusion-induced sustained VF. Measurement of G-proteins revealed that PC led to a reduction of stimulatory Gs proteins, whereas inhibitory Gi proteins were increased. NE (50 nmol) introduced in a manner similar to PC (5 min infusion, 10 min normal perfusion) reduced ischaemic arrhythmias in the same way, as PC. In addition, in NE-pretreated hearts reperfusion induced mostly transient VF, which was spontaneously reverted to a normal sinus rhythm. A transient increase in heart rate and perfusion pressure during NE infusion completely waned before the onset of ischaemia, indicating that antiarrhythmic effect was not related to haemodynamic changes and to conditions of myocardial perfusion. Conclusion: Antiarrhythmic effect of PC may be mediated by a stimulation of adrenergic receptors coupled to appropriate G-proteins. Consequently, the inhibition of adenylate cyclase activity and reduction in cAMP level, as well as the activation of protein kinase C may be considered as two possible pathways leading to a final response.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK

    Tanya Ravingerová, Nigel J. Pyne & James R. Parratt

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  1. Tanya Ravingerová
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  2. Nigel J. Pyne
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  3. James R. Parratt
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Ravingerová, T., Pyne, N.J. & Parratt, J.R. Ischaemic preconditioning in the rat heart: The role of G-proteins and adrenergic stimulation. Mol Cell Biochem 147, 123–128 (1995). https://doi.org/10.1007/BF00944792

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