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Cardiovascular Drugs and Therapy

Erschienen in:

01.02.2011

The Role of β-adrenergic Receptors in the Cardioprotective Effects of Beta-Preconditioning (βPC)

verfasst von: Ruduwaan Salie, Johannes A. Moolman, Amanda Lochner

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 1/2011

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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 cardioprotection.

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Titel: The Role of β-adrenergic Receptors in the Cardioprotective Effects of Beta-Preconditioning (βPC)
verfasst von: Ruduwaan Salie
Johannes A. Moolman
Amanda Lochner
Publikationsdatum: 01.02.2011
Verlag: Springer US
Erschienen in: Cardiovascular Drugs and Therapy / Ausgabe 1/2011
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-010-6275-3

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