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Chronic β1-adrenoceptor blockade impairs ischaemic tolerance and preconditioning in murine myocardium

β-adrenoceptor antagonists are commonly used in ischaemic heart disease (IHD) patients, yet may impair signalling and efficacy of ‘cardioprotective’ interventions. We assessed effects of chronic β1-adrenoceptor antagonism on myocardial resistance to ischaemia-reperfusion (IR) injury and the ability...

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Published in:European journal of pharmacology 2016-10, Vol.789, p.1-7
Main Authors: See Hoe, Louise E., Schilling, Jan M., Busija, Anna R., Haushalter, Kristofer J., Ozberk, Victoria, Keshwani, Malik M., Roth, David M., Toit, Eugene Du, Headrick, John P., Patel, Hemal H., Peart, Jason N.
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container_title European journal of pharmacology
container_volume 789
creator See Hoe, Louise E.
Schilling, Jan M.
Busija, Anna R.
Haushalter, Kristofer J.
Ozberk, Victoria
Keshwani, Malik M.
Roth, David M.
Toit, Eugene Du
Headrick, John P.
Patel, Hemal H.
Peart, Jason N.
description β-adrenoceptor antagonists are commonly used in ischaemic heart disease (IHD) patients, yet may impair signalling and efficacy of ‘cardioprotective’ interventions. We assessed effects of chronic β1-adrenoceptor antagonism on myocardial resistance to ischaemia-reperfusion (IR) injury and the ability of cardioprotective interventions [classic ischaemic preconditioning (IPC); novel sustained ligand-activated preconditioning (SLP)] to reduce IR injury in murine hearts. Young male C57Bl/6 mice were untreated or received atenolol (0.5g/l in drinking water) for 4 weeks. Subsequently, two cardioprotective stimuli were evaluated: morphine pellets implanted (to induce SLP, controls received placebo) 5 days prior to Langendorff heart perfusion, and IPC in perfused hearts (3×1.5min ischaemia/2min reperfusion). Atenolol significantly reduced in vivo heart rate. Untreated control hearts exhibited substantial left ventricular dysfunction (~50% pressure development recovery, ~20mmHg diastolic pressure rise) with significant release of lactate dehydrogenase (LDH, tissue injury indicator) after 25min ischaemia/45min reperfusion. Contractile dysfunction and elevated LDH were reduced >50% with IPC and SLP. While atenolol treatment did not modify baseline contractile function, post-ischaemic function was significantly depressed compared to untreated hearts. Atenolol pre-treatment abolished beneficial effects of IPC, whereas SLP protection was preserved. These data indicate that chronic β1-adrenoceptor blockade can exert negative effects on functional IR tolerance and negate conventional IPC (implicating β1-adrenoceptors in IR injury and IPC signalling). However, novel morphine-induced SLP is resistant to inhibition by β1-adrenoceptor antagonism.
doi_str_mv 10.1016/j.ejphar.2016.06.054
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ispartof European journal of pharmacology, 2016-10, Vol.789, p.1-7
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source ScienceDirect Journals
subjects Adrenergic beta-1 Receptor Antagonists - pharmacology
Animals
Cardiac ischaemia
Cardiovascular drugs
Dose-Response Relationship, Drug
Heart Rate - drug effects
Ischaemia-reperfusion injury
Ischemic Preconditioning, Myocardial
Isoproterenol - pharmacology
L-Lactate Dehydrogenase - metabolism
Male
Mice
Mice, Inbred C57BL
Morphine
Myocardial Reperfusion Injury - enzymology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - physiopathology
Myocardial Reperfusion Injury - therapy
Myocardium - metabolism
Receptors, Adrenergic, beta-1 - metabolism
β-Adrenoceptors
title Chronic β1-adrenoceptor blockade impairs ischaemic tolerance and preconditioning in murine myocardium
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