Myocardial Impact of NHE1 Regulation by Sildenafil

The cardiac Na+/H+ exchanger (NHE1) is a membrane glycoprotein fundamental for proper cell functioning due its multiple housekeeping tasks, including regulation of intracellular pH, Na+ concentration, and cell volume. In the heart, hyperactivation of NHE1 has been linked to the development of differ...

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Autores principales: Escudero, Daiana Sabrina, Pérez, Néstor Gustavo, Díaz, Romina Gisel
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
Materias:
Ciencias Médicas
NHE1
Sildenafil
Intracellular pathways
Cardiac mechanism
PDE5A
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/124326
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-124326
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
NHE1
Sildenafil
Intracellular pathways
Cardiac mechanism
PDE5A
spellingShingle Ciencias Médicas
NHE1
Sildenafil
Intracellular pathways
Cardiac mechanism
PDE5A
Escudero, Daiana Sabrina
Pérez, Néstor Gustavo
Díaz, Romina Gisel
Myocardial Impact of NHE1 Regulation by Sildenafil
topic_facet Ciencias Médicas
NHE1
Sildenafil
Intracellular pathways
Cardiac mechanism
PDE5A
description The cardiac Na+/H+ exchanger (NHE1) is a membrane glycoprotein fundamental for proper cell functioning due its multiple housekeeping tasks, including regulation of intracellular pH, Na+ concentration, and cell volume. In the heart, hyperactivation of NHE1 has been linked to the development of different pathologies. Several studies in animal models that reproduce the deleterious effects of ischemia/reperfusion injury or cardiac hypertrophy have conclusively demonstrated that NHE1 inhibition provides cardioprotection. Unfortunately, NHE1 inhibitors failed to reproduce these effects in the clinical arena. The reasons for those discrepancies are not apparent yet. However, a reasonable clue to consider would be that drugs that completely abolish the exchanger activity, including that its essential housekeeping function may not be the best therapeutic approach. Therefore, interventions tending to specifically reduce its hyperactive state without affecting its basal activity emerge as a novel potential gold standard. In this regard, a promising goal seems to be the modulation of the phosphorylation state of the cytosolic tail of the exchanger. Recent own experiments demonstrated that Sildenafil, a phosphodiesterase 5A inhibitor drug that has been widely used for the treatment of erectile dysfunction is able to decrease NHE1 phosphorylation, and hence reduce its hyperactivity. In connection, growing evidence demonstrates cardioprotective properties of Sildenafil against different cardiac pathologies, with the distinctive characteristic of directly affecting cardiac tissue without altering blood pressure. This mini-review was aimed to focus on the regulation of NHE1 activity by Sildenafil. For this purpose, experimental data reporting Sildenafil effects in different animal models of heart disease will be discussed.
format Articulo
Articulo
author Escudero, Daiana Sabrina
Pérez, Néstor Gustavo
Díaz, Romina Gisel
author_facet Escudero, Daiana Sabrina
Pérez, Néstor Gustavo
Díaz, Romina Gisel
author_sort Escudero, Daiana Sabrina
title Myocardial Impact of NHE1 Regulation by Sildenafil
title_short Myocardial Impact of NHE1 Regulation by Sildenafil
title_full Myocardial Impact of NHE1 Regulation by Sildenafil
title_fullStr Myocardial Impact of NHE1 Regulation by Sildenafil
title_full_unstemmed Myocardial Impact of NHE1 Regulation by Sildenafil
title_sort myocardial impact of nhe1 regulation by sildenafil
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/124326
work_keys_str_mv AT escuderodaianasabrina myocardialimpactofnhe1regulationbysildenafil
AT pereznestorgustavo myocardialimpactofnhe1regulationbysildenafil
AT diazrominagisel myocardialimpactofnhe1regulationbysildenafil
bdutipo_str Repositorios
_version_ 1764820450129477632

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