Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves cardioprotection in the hypoxic myocardium.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_071AE3CEB695
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves cardioprotection in the hypoxic myocardium.
Périodique
Plos One
Auteur(s)
Milano G., Bianciardi P., Rochemont V., Vassalli G., Segesser L.K., Corno A.F., Guazzi M., Samaja M.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2011
Volume
6
Numéro
11
Pages
e27910
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. AIM OF THE STUDY: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O₂) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. CONCLUSIONS: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms.
Mots-clé
Animals, Apoptosis/drug effects, Body Weight/drug effects, Cardiomegaly/blood, Cardiomegaly/complications, Cardiotonic Agents/pharmacology, Cell Hypoxia/drug effects, Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism, Male, Myocardial Infarction/blood, Myocardial Infarction/complications, Myocardium/enzymology, Myocardium/pathology, Nitric Oxide/blood, Nitric Oxide Synthase Type III/metabolism, Oxygen/metabolism, Phosphodiesterase 5 Inhibitors/pharmacology, Polycythemia/blood, Polycythemia/complications, Proto-Oncogene Proteins c-akt/metabolism, Rats, Rats, Sprague-Dawley, Signal Transduction/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/06/2012 18:50
Dernière modification de la notice
20/08/2019 13:29
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