Beneficial effects of chronic pharmacological manipulation of β-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy

Ismayil Ahmet, Melissa Krawczyk, Phillip Heller, Chanil Moon, Edward G. Lakatta, Mark I. Talan

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Background - Studies in isolated cardiac myocytes have demonstrated that signaling via specific β1-adrenergic receptor subtypes (β1ARs) promotes but that signaling via β2ARs protects from cell death. We hypothesized that prolonged β2AR stimulation or β1AR blockade would each protect myocytes from death and thereby ameliorate cardiac remodeling in chronic heart failure. Methods and Results - A large myocardial infarction (MI) induced in rats by coronary artery ligation resulted in a dilated cardiomyopathy (DCM) characterized by infarct expansion and a progressive increase in left ventricular (LV) end-diastolic volume, accompanied by a reduction in ejection fraction (EF), as assessed by repeated echocardiography. Pressure-volume analysis at 8 weeks after ligation showed that diastolic stiffness (Eed) and arterial elastance (Ea) were increased, end-systolic elastance (Ees) was decreased, and arterioventricular (AV) coupling (Ea/Ees) had deteriorated. Apoptosis was present in both peri-infarct and remote myocardium. Chronic (6-week) administration of the β2AR agonists fenoterol or zinterol, starting at 2 weeks after MI, reduced the extent of LV dilation, infarct expansion, and EF decline. The β1AR blocker metoprolol did not affect the former and preserved EF to a lesser extent than did the β2AR agonists. At 8 weeks after ligation, apoptosis was reduced by all drugs but to a greater extent by β2AR agonists than by the β1AR blocker. Both β2AR agonists and the β1AR blocker improved AV coupling, the former mainly by reducing Ea and the latter mainly by increasing Ees. Only the β2AR agonists reduced the Eed and the MI size by reducing infarct expansion. Conclusions - These results provide proof of concept for the efficacy of chronic β2AR stimulation in this DCM model.

Original languageEnglish (US)
Pages (from-to)1083-1090
Number of pages8
Issue number9
StatePublished - Aug 31 2004
Externally publishedYes


  • Heart failure
  • Myocardial infarction
  • Pharmacology
  • Receptors, adrenergic, beta
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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