Please use this identifier to cite or link to this item: http://www.repositorio.ufop.br/jspui/handle/123456789/12078
Title: Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters.
Authors: Hermidorff, Milla Marques
Assis, Leonardo Vinícius Monteiro de
Rodrigues, Joel Alves
Soares, Leôncio Lopes
Andrade, Milton Hércules Guerra de
Natali, Antônio José
Isoldi, Mauro César
Keywords: Adenosine bioavailability
Spironolactone and eplerenone
Rapid effects of aldosterone
Cardioprotection
Cardiac contractility
Issue Date: 2019
Citation: HERMIDORFF, 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.
Abstract: Activation 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.
URI: http://www.repositorio.ufop.br/handle/123456789/12078
metadata.dc.identifier.uri2: https://link.springer.com/article/10.1007/s00380-019-01542-7
metadata.dc.identifier.doi: https://doi.org/10.1007/s00380-019-01542-7
ISSN: 1615-2573
Appears in Collections:DECBI - Artigos publicados em periódicos

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