Abstract | AIMS: METHODS AND RESULTS: Zucker diabetic fatty (ZDF) rats were used as a model of HFpEF and ZDF lean rats served as controls. Animals received vehicle or 10 mg/kg body weight vardenafil per os from weeks 7 to 32 of age. Cardiac function, morphology was assessed by left ventricular (LV) pressure-volume analysis and echocardiography at week 32. Cardiomyocyte force measurements were performed. The key markers of cGMP signalling, nitro-oxidative stress, apoptosis, myocardial hypertrophy and fibrosis were examined. The ZDF animals showed diastolic dysfunction (increased LV/cardiomyocyte stiffness, prolonged LV relaxation time), preserved systolic performance, decreased myocardial cGMP level coupled with impaired protein kinase G (PKG) activity, increased nitro-oxidative stress, enhanced cardiomyocyte apoptosis, and hypertrophic and fibrotic remodelling of the myocardium. Vardenafil effectively prevented the development of HFpEF by maintaining diastolic function (decreased LV/cardiomyocyte stiffness and LV relaxation time), by restoring cGMP levels and PKG activation, by lowering apoptosis and by alleviating nitro-oxidative stress, myocardial hypertrophy and fibrotic remodelling. CONCLUSIONS: We report that vardenafil successfully prevented the development of diabetes mellitus-associated HFpEF. Thus, PDE5A inhibition as a preventive approach might be a promising option in the management of HFpEF patients with diabetes mellitus.
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Authors | Csaba Mátyás, Balázs T Németh, Attila Oláh, Marianna Török, Mihály Ruppert, Dalma Kellermayer, Bálint A Barta, Gábor Szabó, Gábor Kökény, Eszter M Horváth, Beáta Bódi, Zoltán Papp, Béla Merkely, Tamás Radovits |
Journal | European journal of heart failure
(Eur J Heart Fail)
Vol. 19
Issue 3
Pg. 326-336
(03 2017)
ISSN: 1879-0844 [Electronic] England |
PMID | 27995696
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. |
Chemical References |
- Phosphodiesterase 5 Inhibitors
- Vardenafil Dihydrochloride
- Cyclic GMP
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Topics |
- Animals
- Apoptosis
(drug effects)
- Cardiomegaly
(prevention & control)
- Cyclic GMP
(metabolism)
- Diabetes Mellitus, Type 2
(metabolism)
- Echocardiography
- Fibrosis
- Heart
(drug effects)
- Heart Failure
(diagnostic imaging, physiopathology, prevention & control)
- Myocardium
(pathology)
- Myocytes, Cardiac
(drug effects)
- Oxidative Stress
(drug effects)
- Phosphodiesterase 5 Inhibitors
(pharmacology)
- Rats
- Rats, Zucker
- Stroke Volume
- Vardenafil Dihydrochloride
(pharmacology)
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