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Article: β2-adrenergic stimulation attenuates left ventricular remodeling, decreases apoptosis, and improves calcium homeostasis in a rodent model of ischemic cardiomyopathy

Titleβ2-adrenergic stimulation attenuates left ventricular remodeling, decreases apoptosis, and improves calcium homeostasis in a rodent model of ischemic cardiomyopathy
Authors
Issue Date2006
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 2006, v. 317 n. 2, p. 553-561 How to Cite?
AbstractThe benefit of the β2-adrenergic agonist, clenbuterol, in left ventricular assist device patients with dilated cardiomyopathy has been reported, but its effect on ischemic heart failure (HF) is unknown. We investigated whether clenbuterol improves left ventricular remodeling, myocardial apoptosis and has synergy with a β1 antagonist, metoprolol, in a model of ischemic HF. Rats were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF + clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left anterior descending artery (LAD) artery ligation and confirmed by decreased left ventricular fractional shortening, decreased maximum left ventricular dP/dt (dP/dtmax), and elevated left ventricular end-diastolic pressure (LVEDP) compared with sham rats (p < 0.01). After 9 weeks of oral therapy, echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume relationship (EDPVR) measurements were obtained. Immunohistochemistry was performed for myocardial apoptosis and DNA damage markers. Levels of calcium-handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF rats (p < 0.05). The metoprololtreated group had a lower LVEDP and higher dP/dtmax versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had decreased myocardial apoptosis and DNA damage markers and increased DNA repair markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-, metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However, as a combination therapy, there were no synergistic effects of clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR, apoptosis, and calcium homeostasis but does not have synergy with metoprolol in our model of ischemic HF. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/155320
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXydas, Sen_US
dc.contributor.authorKherani, ARen_US
dc.contributor.authorChang, JSen_US
dc.contributor.authorKlotz, Sen_US
dc.contributor.authorHay, Ien_US
dc.contributor.authorMutrie, CJen_US
dc.contributor.authorMoss, GWen_US
dc.contributor.authorGu, Aen_US
dc.contributor.authorSchulman, ARen_US
dc.contributor.authorGao, Den_US
dc.contributor.authorHu, Den_US
dc.contributor.authorWu, EXen_US
dc.contributor.authorWei, Cen_US
dc.contributor.authorOz, MCen_US
dc.contributor.authorWang, Jen_US
dc.date.accessioned2012-08-08T08:32:52Z-
dc.date.available2012-08-08T08:32:52Z-
dc.date.issued2006en_US
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2006, v. 317 n. 2, p. 553-561en_US
dc.identifier.issn0022-3565en_US
dc.identifier.urihttp://hdl.handle.net/10722/155320-
dc.description.abstractThe benefit of the β2-adrenergic agonist, clenbuterol, in left ventricular assist device patients with dilated cardiomyopathy has been reported, but its effect on ischemic heart failure (HF) is unknown. We investigated whether clenbuterol improves left ventricular remodeling, myocardial apoptosis and has synergy with a β1 antagonist, metoprolol, in a model of ischemic HF. Rats were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF + clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left anterior descending artery (LAD) artery ligation and confirmed by decreased left ventricular fractional shortening, decreased maximum left ventricular dP/dt (dP/dtmax), and elevated left ventricular end-diastolic pressure (LVEDP) compared with sham rats (p < 0.01). After 9 weeks of oral therapy, echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume relationship (EDPVR) measurements were obtained. Immunohistochemistry was performed for myocardial apoptosis and DNA damage markers. Levels of calcium-handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF rats (p < 0.05). The metoprololtreated group had a lower LVEDP and higher dP/dtmax versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had decreased myocardial apoptosis and DNA damage markers and increased DNA repair markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-, metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However, as a combination therapy, there were no synergistic effects of clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR, apoptosis, and calcium homeostasis but does not have synergy with metoprolol in our model of ischemic HF. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.en_US
dc.languageengen_US
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_US
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_US
dc.subject.meshAdrenergic Beta-Agonists - Pharmacologyen_US
dc.subject.meshAdrenergic Beta-Antagonists - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshBody Weight - Drug Effectsen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshDna Damageen_US
dc.subject.meshDna Repairen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshEchocardiographyen_US
dc.subject.meshHemodynamics - Drug Effectsen_US
dc.subject.meshHomeostasis - Drug Effectsen_US
dc.subject.meshMyocardial Ischemia - Drug Therapy - Metabolism - Pathology - Physiopathologyen_US
dc.subject.meshOrgan Size - Drug Effectsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptors, Adrenergic, Beta - Metabolismen_US
dc.subject.meshVentricular Remodeling - Drug Effectsen_US
dc.titleβ2-adrenergic stimulation attenuates left ventricular remodeling, decreases apoptosis, and improves calcium homeostasis in a rodent model of ischemic cardiomyopathyen_US
dc.typeArticleen_US
dc.identifier.emailWu, EX:ewu1@hkucc.hku.hken_US
dc.identifier.authorityWu, EX=rp00193en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1124/jpet.105.099432en_US
dc.identifier.pmid16421285-
dc.identifier.scopuseid_2-s2.0-33645857987en_US
dc.identifier.hkuros119801-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33645857987&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume317en_US
dc.identifier.issue2en_US
dc.identifier.spage553en_US
dc.identifier.epage561en_US
dc.identifier.isiWOS:000236885000012-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridXydas, S=6507448586en_US
dc.identifier.scopusauthoridKherani, AR=7003436417en_US
dc.identifier.scopusauthoridChang, JS=13002880300en_US
dc.identifier.scopusauthoridKlotz, S=9844521200en_US
dc.identifier.scopusauthoridHay, I=7101789694en_US
dc.identifier.scopusauthoridMutrie, CJ=6506958369en_US
dc.identifier.scopusauthoridMoss, GW=35920464600en_US
dc.identifier.scopusauthoridGu, A=7006612957en_US
dc.identifier.scopusauthoridSchulman, AR=7005308371en_US
dc.identifier.scopusauthoridGao, D=7202964904en_US
dc.identifier.scopusauthoridHu, D=13003262800en_US
dc.identifier.scopusauthoridWu, EX=7202128034en_US
dc.identifier.scopusauthoridWei, C=7401658197en_US
dc.identifier.scopusauthoridOz, MC=7102364376en_US
dc.identifier.scopusauthoridWang, J=8061150000en_US

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