BACKGROUND AND PURPOSEThe 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).
EXPERIMENTAL APPROACHWe 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 ; HF + metoprolol + indacaterol. All pharmacological treatments continued for 15 weeks.
KEY RESULTSTreatment 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.
CONCLUSION AND IMPLICATIONSThe 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.
AbbreviationsANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; EF, ejection fraction (%); GRK2, GPCR kinase 2; HF, heart failure; LV, left ventricular; LVIDd, LV diastolic internal diameter; LVIDs, LV systolic internal diameter