A denosine A2A receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction

Background: This work evaluated the hypothesis that 3,4-methylenedioxybenzoyl-2thienylhydrazone (LASSBio-294), an agonist of adenosine A(2A) receptor, could be beneficial for preventing cardiac dysfunction due to hypertension associated with myocardial infarction (MI). Methods: Male spontaneously hypertensive rats (SHR) were randomly divided into four groups (six animals per group): sham-operation (SHR-Sham), and myocardial infarction rats (SHR-MI) were treated orally either with vehicle or LASSBio-294 (10 and 20 mg. kg(-1).d(-1)) for 4 weeks. Echocardiography and in vivo hemodynamic parameters measured left ventricle (LV) structure and function. Exercise tolerance was evaluated using a treadmill test. Cardiac remodeling was accessed by LV collagen deposition and tumor necrosis factor a expression. Results: Early mitral inflow velocity was significantly reduced in the SHR-MI group, and there was significant recovery in a dose-dependent manner after treatment with LASSBio-294. Exercise intolerance observed in the SHR-MI group was prevented by 10 mg. kg(-1).d(-1) of LASSBio-294, and exercise tolerance exceeded that of the SHR-Sham group at 20 mg. kg(-1).d(-1). LV end-diastolic pressure increased after MI, and this was prevented by 10 and 20 mg. kg(-1).d(-1) of LASSBio-294. Sarcoplasmic reticulum Ca2+ ATPase levels were restored in a dose-dependent manner after treatment with LASSBio-294. Fibrosis and inflammatory processes were also counteracted by LASSBio-294, with reductions in LV collagen deposition and tumor necrosis factor a expression. Conclusion: In summary, oral administration of LASSBio-294 after MI in a dose-dependent manner prevented the development of cardiac dysfunction, demonstrating this compound's potential as an alternative treatment for heart failure in the setting of ischemic heart disease with superimposed chronic hypertension.