Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na<SUP>+</SUP>/H<SUP>+</SUP> exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papilla...

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Autores principales: Pérez, Néstor Gustavo, Piaggio, Martín Roberto, Ennis, Irene Lucía, Garciarena, Carolina Denis, Morales, Celina, Escudero, Eduardo Manuel, Cingolani, Oscar H., Chiappe de Cingolani, Gladys Ethel, Yang, Xiao Ping, Cingolani, Horacio Eugenio
Formato: Articulo
Lenguaje:Inglés
Publicado: 2007
Materias:
Ciencias Médicas
Basic science
Hypertrophy/remodeling
Membrane transport/ion channels
Myocardial infarction
Na+/H+ exchanger
PDE5A inhibition
Physiology/function
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84866
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84866
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
Basic science
Hypertrophy/remodeling
Membrane transport/ion channels
Myocardial infarction
Na+/H+ exchanger
PDE5A inhibition
Physiology/function
spellingShingle Ciencias Médicas
Basic science
Hypertrophy/remodeling
Membrane transport/ion channels
Myocardial infarction
Na+/H+ exchanger
PDE5A inhibition
Physiology/function
Pérez, Néstor Gustavo
Piaggio, Martín Roberto
Ennis, Irene Lucía
Garciarena, Carolina Denis
Morales, Celina
Escudero, Eduardo Manuel
Cingolani, Oscar H.
Chiappe de Cingolani, Gladys Ethel
Yang, Xiao Ping
Cingolani, Horacio Eugenio
Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction
topic_facet Ciencias Médicas
Basic science
Hypertrophy/remodeling
Membrane transport/ion channels
Myocardial infarction
Na+/H+ exchanger
PDE5A inhibition
Physiology/function
description Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na<SUP>+</SUP>/H<SUP>+</SUP> exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg<SUP>-1</SUP> day<SUP>-1</SUP>) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.
format Articulo
Articulo
author Pérez, Néstor Gustavo
Piaggio, Martín Roberto
Ennis, Irene Lucía
Garciarena, Carolina Denis
Morales, Celina
Escudero, Eduardo Manuel
Cingolani, Oscar H.
Chiappe de Cingolani, Gladys Ethel
Yang, Xiao Ping
Cingolani, Horacio Eugenio
author_facet Pérez, Néstor Gustavo
Piaggio, Martín Roberto
Ennis, Irene Lucía
Garciarena, Carolina Denis
Morales, Celina
Escudero, Eduardo Manuel
Cingolani, Oscar H.
Chiappe de Cingolani, Gladys Ethel
Yang, Xiao Ping
Cingolani, Horacio Eugenio
author_sort Pérez, Néstor Gustavo
title Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction
title_short Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction
title_full Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction
title_fullStr Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction
title_full_unstemmed Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction
title_sort phosphodiesterase 5a inhibition induces na+/h+ exchanger blockade and protection against myocardial infarction
publishDate 2007
url http://sedici.unlp.edu.ar/handle/10915/84866
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