Advanced search
Start date
Betweenand
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
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]
Total Authors: 7
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: HEART AND VESSELS; v. 35, n. 5, p. 719-730, MAY 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 13/24337-4 - Clock genes modulation by UVA/blue light stimulation in normal melan-A and transformed B-16 melanocytes
Grantee:Leonardo Vinícius Monteiro de Assis
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/16511-8 - Involvement of the photosensitive and temporal controlling systems in the development, progression, and metastasis of malignant melanoma: an investigation of novel therapeutic targets
Grantee:Leonardo Vinícius Monteiro de Assis
Support Opportunities: Scholarships in Brazil - Post-Doctoral