Hermidorff, Milla MarquesAssis, Leonardo Vinícius Monteiro deRodrigues, Joel AlvesSoares, Leôncio LopesAndrade, Milton Hércules Guerra deNatali, Antônio JoséIsoldi, Mauro César2020-04-172020-04-172019HERMIDORFF, M. M. et al. Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters. Heart and Vessels, v. 35, p. 719–730, dez. 2019. Disponível em: <https://link.springer.com/article/10.1007/s00380-019-01542-7>. Acesso em: 10 fev. 2020.1615-2573http://www.repositorio.ufop.br/handle/123456789/12078Activation of mineralocorticoid receptor antagonists (MRAs) is cardioprotective; however, this property is lost upon blockade or inactivation of adenosine (ADO) receptor A2b. In this study, we investigated whether the effects of MRAs are mediated by an interaction between cardioprotective ADO receptors A1 and A3. 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 A1 or A3 antagonists compared to control groups. Upon co-treatment with MRAs, EPL and SPI fully and partially reverted the effects of receptor A1 or A3 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 A1 and A3.en-USrestritoAdenosine bioavailabilitySpironolactone and eplerenoneRapid effects of aldosteroneCardioprotectionCardiac contractilityArtigo publicado em periodicohttps://link.springer.com/article/10.1007/s00380-019-01542-7https://doi.org/10.1007/s00380-019-01542-7