title: Adenosine A2Areceptor 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 A2Areceptor, 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-1of 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-1of 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.
  
  
  CONCLUSIONS
  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.affiliation: Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Gabriel-Costa
authors.affiliation: Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Roberto T
authors.initials: RT
authors.lastname: Sudo
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Emanuele B
authors.initials: EB
authors.lastname: Ferraz
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: José Hamilton M
authors.initials: JH
authors.lastname: Nascimento
authors.affiliation: Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carlos Alberto M
authors.initials: CA
authors.lastname: Fraga
authors.affiliation: Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.affiliation: Research Program Development of Drugs, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control*; D006835:Hydrazones / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D006835:Hydrazones; C439284:LASSBio 294; D013876:Thiophenes
keywords: LASSBio-294 and agonist of adenosine A2A receptor; hypertension; myocardial infarction