Pharmacological stimulation of β2-adrenergic receptors (β2AR) enhances therapeutic effectiveness of β1AR blockade in rodent dilated ischemic cardiomyopathy

Ismayil Ahmet, Edward G. Lakatta, Mark I. Talan

Research output: Contribution to journalArticlepeer-review

Abstract

Background. We have reported that β2 adrenoreceptor (β2AR) stimulation is anti-apoptotic, and has strong beneficial effect on cardiac remodeling in an experimental model of post myocardial infarction chronic heart failure (CHF) in rats. Here we investigate whether the addition of chronic pharmacological β2AR stimulation enhances the therapeutic effects of β1AR blockade on cardiac remodeling in the same model. Methods and results. Metoprolol, β1AR blocker, given alone (β1) or in combination with β2AR agonist, fenoterol (β1β2) were administered to rats via drinking water for 6 weeks, beginning 2 weeks following permanent coronary ligation. Progressive left ventricular (LV) remodeling of untreated animals, assessed by repeated echocardiography, occurred during the observation time, i.e., 42% and 25% increases in end-systolic and end-diastolic LV volumes respectively, 27% fall in ejection fraction, and 35% infarct expansion. Pressure-volume loop analyses at 2d and 8th post infarction weeks showed continuous deterioration of systolic and diastolic functions and arterio-ventricular mismatch. Histological evaluation at the end of 8 weeks revealed the MI expansion and hypertrophy of cardiomyocytes. β1β2 prevented LV emodeling, MI expansion and cardiomyocytes hypertrophy to a greater degree than β1, due, in large part, to a vasodilatory effect of β2AR stimulation and thus improvement of arterio-ventricular mismatch. The abnormal diastolic performance improved only in β1 β2. β1 β2 treatment reduced myocardial apoptosis throughout myocardium, but β1 reduced apoptopsis only in the areas remote from MI. Conclusion. The therapeutic effects of chronic β1AR blockade on cardiac remodeling of heart failure are enhanced and extended when supplemented with β2AR stimulation.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalHeart Failure Reviews
Volume10
Issue number4
DOIs
StatePublished - Dec 2005
Externally publishedYes

Keywords

  • Chronic heart failure
  • Left ventricular remodeling
  • Myocardial infarction
  • Rat
  • β-adrenergic receptor subtypes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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