Concomitant phosphodiesterase 5 inhibition enhances myocardial protection by inhaled nitric oxide in ischemia-reperfusion injurys

Arpad Lux, Peter Pokreisz, Melissa Swinnen, Ellen Caluwe, Hilde Gillijns, Zsolt Szelid, B. Merkely, Stefan P. Janssens

Research output: Contribution to journalArticle

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Abstract

Enhanced cyclic guanosine monophosphate (cGMP) signaling may attenuate myocardial ischemia-reperfusion injury (I/R) and improve left ventricular (LV) functional recovery after myocardial infarction (MI). We investigated the cardioprotection afforded by inhaled NO (iNO), the phosphodiesterase 5 (PDE5)-specific inhibitor tadalafil (TAD), or their combination (iNO1TAD) in C57Bl6J mice subjected to 6-minute left anterior descending artery ligation followed by reperfusion. We measured plasma and cardiac concentrations of cGMP during early reperfusion, quantified myocardial necrosis and inflammation by serial troponin-I (TnI) and myeloperoxidase-positive cell infiltration at day 3, and evaluated LV function and remodeling after 4 weeks using echocardiography and pressure-conductance catheterization. Administration of iNO, TAD, or both during I/R was safe and hemodynamically well tolerated. Compared with untreated mice (CON), only iNO1TADincreased plasmaand cardiac-cGMP levels during early reperfusion (80 ± 12 versus 36 ± pmol/ml and 0.1560.02 versus 0.0560.01 pmol/mg protein, P

Original languageEnglish
Pages (from-to)284-292
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume356
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Type 5 Cyclic Nucleotide Phosphodiesterases
Cyclic GMP
Reperfusion
Nitric Oxide
Ischemia
Myocardial Reperfusion Injury
Phosphodiesterase 5 Inhibitors
Myocardial Reperfusion
Ventricular Remodeling
Troponin I
Reperfusion Injury
Left Ventricular Function
Catheterization
Peroxidase
Myocardial Ischemia
Ligation
Echocardiography
Necrosis
Arteries
Myocardial Infarction

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Concomitant phosphodiesterase 5 inhibition enhances myocardial protection by inhaled nitric oxide in ischemia-reperfusion injurys. / Lux, Arpad; Pokreisz, Peter; Swinnen, Melissa; Caluwe, Ellen; Gillijns, Hilde; Szelid, Zsolt; Merkely, B.; Janssens, Stefan P.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 356, No. 2, 01.02.2016, p. 284-292.

Research output: Contribution to journalArticle

Lux, Arpad ; Pokreisz, Peter ; Swinnen, Melissa ; Caluwe, Ellen ; Gillijns, Hilde ; Szelid, Zsolt ; Merkely, B. ; Janssens, Stefan P. / Concomitant phosphodiesterase 5 inhibition enhances myocardial protection by inhaled nitric oxide in ischemia-reperfusion injurys. In: Journal of Pharmacology and Experimental Therapeutics. 2016 ; Vol. 356, No. 2. pp. 284-292.
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