Drug Design, Development and Therapy (Nov 2024)
Novel Agonists of Adenosine Receptors in Animal Model of Acute Myocardial Infarction
Abstract
Fabricio Beltrame,1,2 Bianca Nascimento-Carlos,3 Jaqueline S da Silva,1,3 Rodolfo Couto Maia,4 Tadeu Lima Montagnoli,3,4 Eliezer J Barreiro3,4 ,† Gisele Zapata-Sudo1– 4 1Programa de Pós-Graduação em Medicina (Cardiologia), Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Instituto do Coração Edson Saad, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 3Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 4Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil†Professor Eliezer Barreiro passed away on April 8, 2024Correspondence: Gisele Zapata-Sudo, Universidade Federal do Rio de Janeiro, Instituto do Coração Edson Saad, Faculdade de Medicina, Centro de Ciências da Saúde, Bloco J, Sala 11, Rio de Janeiro, RJ, 21941-902, Brasil, Tel/Fax +55-21-39386505, Email [email protected]; [email protected] and Purpose: Current treatments for acute myocardial infarction (AMI) include pain relief and attempts to improve survival. This study investigated the effects of two new ligands of the adenosine receptor, LASSBio-1027 and LASSBio-1860, on cardiac function in an experimental model of AMI.Methods: AMI was induced in Wistar rats by ligating the anterior descending coronary arteries. Infarcted animals were treated orally with vehicle (DMSO), LASSBio-1027 (30 and 70 μmol/kg), or LASSBio-1860 (70 μmol/kg) for seven days. Hemodynamic parameters were observed using echocardiography, whereas inflammation and fibrosis were detected using histological analysis.Results: MI increased the filling pressure from 23.0 ± 1.6 and 14.0 ± 2.0 to 37.0 ± 3.7 and 33.2 ± 8.0, respectively indicating diastolic dysfunction. However, treatment with LASSBio-1027 (70 μmol/kg) and LASSBio-1860 (70 μmol/kg) reduced this parameter to 23.9 ± 5.4 and 17.1 ± 6.7. An impairment in ejection fraction from 57.1 ± 3.2 to 36.6 ± 2.0% was observed after MI, partially recovered to 47.0 ± 7.4% by LASSBio-1027 and fully restored to 61.8 ± 4.3% after 7 days of treatment with LASSBio-1860. After MI, collagen deposition in LV free wall was increased to 31.4 ± 11.0% and treatment with LASSBio-1027 reduced to 23.4 ± 6.0 and 19.7 ± 8.0% at 30 and 70 μmol/kg, respectively. Similarly, LASSBio-1860 reduced collagen levels to 63.1 ± 2.0%.Conclusion: Fibrosis and inflammatory components of MI reduced following treatment with agonist of adenosine receptor subtype A2A. Cardiac remodeling induced by LASSBio-1027 and LASSBio-1860 may be responsible for the improvement in cardiac function in AMI through the activation of A2A adenosine receptors.Keywords: cardiac remodeling, inflammation, myocardial infarction, adenosine receptors
