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

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dc.contributor.authorHermidorff, Milla Marques
dc.contributor.authorAssis, Leonardo Vinícius Monteiro de
dc.contributor.authorRodrigues, Joel Alves
dc.contributor.authorSoares, Leôncio Lopes
dc.contributor.authorAndrade, Milton Hércules Guerra de
dc.contributor.authorNatali, Antônio José
dc.contributor.authorIsoldi, Mauro César
dc.date.accessioned2020-04-17T14:04:30Z
dc.date.available2020-04-17T14:04:30Z
dc.date.issued2019
dc.description.abstractActivation 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.pt_BR
dc.identifier.citationHERMIDORFF, 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.pt_BR
dc.identifier.doihttps://doi.org/10.1007/s00380-019-01542-7pt_BR
dc.identifier.issn1615-2573
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/12078
dc.identifier.uri2https://link.springer.com/article/10.1007/s00380-019-01542-7pt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectAdenosine bioavailabilitypt_BR
dc.subjectSpironolactone and eplerenonept_BR
dc.subjectRapid effects of aldosteronept_BR
dc.subjectCardioprotectionpt_BR
dc.subjectCardiac contractilitypt_BR
dc.titleMineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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