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.
journal_name
Heart Vesselsjournal_title
Heart and vesselsauthors
Hermidorff MM,de Assis LVM,Rodrigues JA,Soares LL,Andrade MHG,Natali AJ,Isoldi MCdoi
10.1007/s00380-019-01542-7subject
Has Abstractpub_date
2020-05-01 00:00:00pages
719-730issue
5eissn
0910-8327issn
1615-2573pii
10.1007/s00380-019-01542-7journal_volume
35pub_type
杂志文章abstract::In order to clarify the pathogenesis of acute myocardial infarction (MI) in hearts with normal coronary arteries, infarct size, and the extent of contraction band necrosis (CBN), coagulation necrosis, and hemorrhage were quantitatively examined using an image analyzer in 5 autopsy cases of MI with normal or nearly nor...
journal_title:Heart and vessels
pub_type: 杂志文章
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journal_title:Heart and vessels
pub_type: 杂志文章
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journal_title:Heart and vessels
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doi:10.1007/s00380-007-0998-5
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journal_title:Heart and vessels
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journal_title:Heart and vessels
pub_type: 临床试验,杂志文章
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doi:10.1007/s00380-010-0058-4
更新日期:2011-07-01 00:00:00
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journal_title:Heart and vessels
pub_type: 杂志文章
doi:10.1007/s00380-006-0939-8
更新日期:2007-03-01 00:00:00
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journal_title:Heart and vessels
pub_type: 杂志文章,多中心研究
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更新日期:2016-10-01 00:00:00
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journal_title:Heart and vessels
pub_type: 杂志文章
doi:10.1007/s00380-016-0928-5
更新日期:2017-04-01 00:00:00
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journal_title:Heart and vessels
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doi:10.1007/s00380-019-01413-1
更新日期:2019-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s00380-014-0515-6
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journal_title:Heart and vessels
pub_type: 杂志文章
doi:10.1007/s00380-006-0930-4
更新日期:2007-01-01 00:00:00
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doi:10.1007/s00380-020-01575-3
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journal_title:Heart and vessels
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更新日期:1997-01-01 00:00:00
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journal_title:Heart and vessels
pub_type: 杂志文章,多中心研究
doi:10.1007/s00380-018-1137-1
更新日期:2018-08-01 00:00:00
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journal_title:Heart and vessels
pub_type: 杂志文章
doi:10.1007/s00380-018-1235-0
更新日期:2019-02-01 00:00:00
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journal_title:Heart and vessels
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pub_type: 杂志文章,随机对照试验
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journal_title:Heart and vessels
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journal_title:Heart and vessels
pub_type: 杂志文章
doi:10.1007/BF02058280
更新日期:1991-01-01 00:00:00
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journal_title:Heart and vessels
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更新日期:2015-05-01 00:00:00
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doi:10.1007/s00380-009-1218-2
更新日期:2010-09-01 00:00:00
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journal_title:Heart and vessels
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journal_title:Heart and vessels
pub_type: 临床试验,杂志文章
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journal_title:Heart and vessels
pub_type: 杂志文章
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更新日期:2010-05-01 00:00:00