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

Abstract

BACKGROUND:

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).

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 α 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 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 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 α 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.

• Authors: 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
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 11 Pg. 553-562 ( 2017) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 28293100 (Publication Type: Journal Article)

Chemical References

• Adenosine A2 Receptor Agonists
• Hydrazones
• LASSBio 294
• Thiophenes

Topics

• Adenosine A2 Receptor Agonists (administration & dosage, therapeutic use)
• Administration, Oral
• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Heart Failure (complications, physiopathology, prevention & control)
• Hydrazones (administration & dosage, therapeutic use)
• Male
• Myocardial Infarction (complications, pathology, physiopathology)
• Rats
• Rats, Inbred SHR
• Thiophenes (administration & dosage, therapeutic use)