The role of β-adrenergic receptors in the cardioprotective effects of beta-preconditioning (βPC)
Date
2011
Authors
Salie R.
Moolman J.A.
Lochner A.
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Journal ISSN
Volume Title
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Abstract
Aim To determine the mechanism whereby transient stimulation of the β-adrenergic receptor subtypes (β-AR) elicit cardioprotection against subsequent ischaemia. Methods Isolated rat hearts were subjected to 35 min regional ischaemia (RI) and reperfusion and infarct size (IS) determined. Hearts were preconditioned with 5 min isoproterenol (β1/β2-AR agonist), denopamine (β1-AR agonist), formoterol hemifumarate (β2-AR agonist) or BRL37344 (β3-AR agonist) and 5 min reperfusion. The roles of the β-ARs, NO, PKA, and PI3-K were explored by using selective antagonists/blockers. Pertussis toxin was administered i.p., 48 h prior to experimentation. Results IS of hearts preconditioned with either isoproterenol, denopamine or formoterol (% of area at risk: 23.6 ± 1.26; 24.52 ± 0.89; 20.74 ± 0.85 respectively) were significantly smaller than that of non-preconditioned hearts (41.7 ± 1.65) and associated with improvement in postischaemic mechanical performance. The β3-AR agonist BRL37344 could not reduce IS. The β1- and β2-AR blockers CGP-20712A and ICI-118551 abolished the reduction in IS and improvement in mechanical recovery during reperfusion induced by isoproterenol preconditioning, while the β3-AR blocker SR59230A was without effect. Both Rp-8-CPT-cAMPs and wortmannin significantly increased IS when administered before and during β1/β2-AR preconditioning and reduced mechanical recovery. PTX pretreatment had no significant effect on the reduction in IS induced by β1/β2-AR or β2-AR preconditioning, but reduced mechanical recovery in β2-AR preconditioning. Similarly the NOS inhibitors L-NAME and LNNA had no effect on IS in β1/β2-AR preconditioning, but depressed mechanical recovery. Conclusion Protection afforded by β-ARs stimulation, depends on activation of both β1-AR and β2-ARs but not β3-AR. With functional recovery as endpoint, results suggest involvement of NO in β1/β2-AR preconditioning and the Gi protein in β2-AR preconditioning. Both PKA and PI3-K activation were essential for β1/β2-AR cardio-protection. © Springer Science+Business Media, LLC 2010.
Description
Keywords
β-adrenergic receptors; Gi protein; Infarct size; Mechanical recovery during reperfusion; Protein kinase A, beta adrenergic receptor; cyclic AMP dependent protein kinase; denopamine; formoterol fumarate; inhibitory guanine nucleotide binding protein; isoprenaline; nitric oxide; nitric oxide synthase; phosphatidylinositol 3 kinase; animal tissue; article; clinical protocol; controlled study; enzyme activation; heart infarction size; heart muscle ischemia; heart muscle reperfusion; heart protection; ischemic preconditioning; isolated heart; male; nonhuman; priority journal; protein function; rat; A Kinase Anchor Proteins; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Ethanolamines; GTP-Binding Protein alpha Subunits, Gi-Go; Heart; Ischemic Preconditioning, Myocardial; Isoproterenol; Male; Myocardial Reperfusion Injury; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phosphatidylinositol 3-Kinases; Rats; Rats, Wistar; Receptors, Adrenergic, beta
Citation
Cardiovascular Drugs and Therapy
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