A denosine A(2A) receptor agonist prevents cardiac remodeling and dysfunction in spontaneously hypertensive male rats after myocardial infarction

作者：da Silva Jaqueline S; Gabriel Costa Daniele; Sudo Roberto T; Wang Hao; Groban Leanne; Ferraz Emanuele B; Nascimento Jose Hamilton M; Fraga Carlos Alberto M; Barreiro Eliezer J; Zapata Sudo Gisele^*

来源：Drug Design, Development and Therapy, 2017, 11: 553-562.

DOI：10.2147/dddt.s113289

• hypertension
• myocardial infarction
• LASSBio-294 and agonist of adenosine A(2A) receptor

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.

• 出版日期2017