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Heart and Vessels
Published in: Heart and Vessels 5/2020

01-05-2020 | Spironolactone | Original Article

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

Authors: Milla Marques Hermidorff, Leonardo Vinícius Monteiro de Assis, Joel Alves Rodrigues, Leôncio Lopes Soares, Milton Hércules Guerra Andrade, Antônio José Natali, Mauro Cesar Isoldi

Published in: Heart and Vessels | Issue 5/2020

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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.
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Metadata
Title
Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters
Authors
Milla Marques Hermidorff
Leonardo Vinícius Monteiro de Assis
Joel Alves Rodrigues
Leôncio Lopes Soares
Milton Hércules Guerra Andrade
Antônio José Natali
Mauro Cesar Isoldi
Publication date
01-05-2020
Publisher
Springer Japan
Published in
Heart and Vessels / Issue 5/2020
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-019-01542-7

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