Jaqueline S da Silva, Daniele Gabriel-Costa, Roberto T Sudo, Hao Wang, Leanne Groban, Emanuele B Ferraz, José Hamilton M Nascimento, Carlos Alberto M Fraga, Eliezer J Barreiro, Gisele Zapata-Sudo

This work evaluated the hypothesis that 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294), an agonist of adenosine A2A receptor, could be beneficial for preventing cardiac dysfunction due to hypertension associated with myocardial infarction (MI). 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 α expression. 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 LASS-Bio-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 Ca(2+) 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 α expression. 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.