Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters

Autor(es)

Hermidorff, Milla Marques ^[1] ; Monteiro de Assis, Leonardo Vinicius ^[2] ; Rodrigues, Joel Alves ^[3] ; Soares, Leoncio Lopes ^[3] ; Guerra Andrade, Milton Hercules ^[4] ; Natali, Antonio Jose ^[3] ; Isoldi, Mauro Cesar ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Ouro Preto, Res Ctr Biol Sci, Inst Exact & Biol Sci, Cell Signaling Lab, Campus Morro do Cruzeiro, BR-35400000 Ouro Preto, MG - Brazil

^[2] Univ Sao Paulo, Inst Biosci, Dept Physiol, Lab Comparat Physiol Pigmentat, Sao Paulo - Brazil

^[3] Univ Fed Vicosa, Dept Phys Educ, Lab Exercise Biol, Vicosa, MG - Brazil

^[4] Univ Fed Ouro Preto, Res Ctr Biol Sci, Inst Exact & Biol Sci, Lab Enzymol & Prote, Ouro Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: HEART AND VESSELS; v. 35, n. 5, p. 719-730, MAY 2020.
• Citações Web of Science: 0

Resumo

Activation of mineralocorticoid receptor antagonists (MRAs) is cardioprotective; however, this property is lost upon blockade or inactivation of adenosine (ADO) receptor A(2b). In this study, we investigated whether the effects of MRAs are mediated by an interaction between cardioprotective ADO receptors A(1) and A(3). Spironolactone (SPI) or eplerenone (EPL) increased ADO levels in the plasma of treated animals compared to control animals. SPI or EPL increased the protein and activity levels of ecto-5 `-nucleotidase (NT5E), an enzyme that synthesizes ADO, compared to control. The levels of ADO deaminase (ADA), which degrades ADO, were not affected by SPI or EPL; however, the activity of ADA was reduced in SPI-treated rats compared to control. Using an isolated cardiomyocyte model, we found inotropic and chronotropic effects, and increased calcium transient {[}Ca2+](i) in cells treated with ADO receptor A(1) or A(3) antagonists compared to control groups. Upon co-treatment with MRAs, EPL and SPI fully and partially reverted the effects of receptor A(1) or A(3) antagonism, respectively. Collectively, MRAs in vivo lead to increased ADO bioavailability. In vitro, the rapid effects of SPI and EPL are mediated by an interaction between ADO receptors A(1) and A(3). (AU)

• Processo FAPESP: 13/24337-4 - Mecanismos de modulação de genes de relógio em melanócitos normais (melan-A) e transformados (melanoma B16-F10) por UVA e luz azul
• Beneficiário: Leonardo Vinícius Monteiro de Assis
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/16511-8 - Participação dos sistemas de fotorrecepção e de controle temporal no desenvolvimento, progressão e metástase do melanoma maligno: investigação de novos alvos terapêuticos
• Beneficiário: Leonardo Vinícius Monteiro de Assis
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado