title: Effects of chronic treatment with the new ultra-long-acting β2 -adrenoceptor agonist indacaterol alone or in combination with the β1 -adrenoceptor blocker metoprolol on cardiac remodelling.
abstract: OBJECTIVE
  The ability of a chronic treatment with indacaterol, a new ultra-long-acting β2 -adrenoceptor agonist, to reverse cardiac remodelling and its effects in combination with metoprolol, a selective β1 -adrenoceptor antagonist, were investigated on myocardial infarction in a rat model of heart failure (HF).
  
  
  METHODS
  We investigated the effects of indacaterol and metoprolol, administered alone or in combination, on myocardial histology, β-adrenoceptor-mediated pathways, markers of remodelling and haemodynamic parameters in a rat model of HF. Five groups of rats were assessed: sham-operated rats; HF rats; HF + indacaterol 0.3 mg·kg(-1) ·day(-1) ; HF + metoprolol 100 mg·kg(-1) ·day(-1) ; HF + metoprolol + indacaterol. All pharmacological treatments continued for 15 weeks.
  
  
  RESULTS
  Treatment with either indacaterol or metoprolol significantly reduced the infarct size in HF rats. However, the combination of indacaterol and metoprolol reduced the infarct size even further, reduced both BP and heart rate, reversed the decrease in ejection fraction, normalized left ventricular systolic and diastolic internal diameters, normalized the decreased β1 adrenoceptor mRNA expression as well as cardiac cAMP levels and reduced cardiac GPCR kinase 2 expression, compared with the untreated HF group.
  
  
  CONCLUSIONS
  The results of our study demonstrated an additive interaction between indacaterol and metoprolol in normalizing and reversing cardiac remodelling in our experimental model of HF. The translation of these findings to clinical practice might be of interest, as this combination of drugs could be safer and more effective in patients suffering from HF and COPD.
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.|Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Second University of Naples, Naples, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rinaldi
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Donniacuo
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Sodano
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gritti
authors.affiliation: Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Martuscelli
authors.affiliation: Anatomic Pathology, Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.|Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Second University of Naples, Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Rafaniello
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.|Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Second University of Naples, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.|Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Second University of Naples, Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capuano
authors.affiliation: Centre of Excellence for Cardiovascular Diseases, Second University of Naples, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D007189:Indans; D015363:Quinolones; D011943:Receptors, Adrenergic, beta; C510790:indacaterol; D008790:Metoprolol
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