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Basic Res Cardiol. 2012 Nov;107(6):308. doi: 10.1007/s00395-012-0308-y. Epub 2012 Nov 2.

Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo.

Author information

1
Department of Cardiology and Pneumology, Campus Benjamin Franklin (CBF), Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. dirk.westermann@web.de

Erratum in

  • Basic Res Cardiol. 2013 Mar;108(2):327.

Abstract

Sildenafil inhibits cyclic GMP-specific phosphodiesterase type-5A (PDE5A) and can prevent cardiac hypertrophy and left ventricular (LV) dysfunction in mice subjected to severe pressure-overload. The pathophysiological role of sildenafil in adverse remodeling in the hypertensive heart after chronic renin-angiotensin aldosterone system stimulation is unknown. Therefore, we studied the efficacy of the PDE5A inhibitor sildenafil for treating advanced cardiac hypertrophy and LV remodeling due to angiotensin (Ang)II-induced heart failure (HF) in vivo. C57BL6/J mice were subjected to AngII-induced cardiac hypertrophy for 3 weeks and cardiac dysfunction, cardiac inflammatory stress response, adverse remodeling as well as apoptosis were documented. Mice were subsequently treated with sildenafil (100 mg/kg/day) or placebo with delay of 5 days for treating AngII infusion-induced adverse events. Compared to controls, AngII infusion resulted in impaired systolic (dP/dt (max) -46 %, SV -16 %, SW -43 %, E (a) +51 %, EF -37 %, CO -36 %; p < 0.05) and diastolic (dP/dt (min) -36 %, LV end diastolic pressure +73 %, Tau +21 %, stiffness constant β +74 %; p < 0.05) LV function. This was associated with a significant increase in cardiac hypertrophy and fibrosis. Increased inflammatory response was also indicated by an increase in immune cell infiltration and apoptosis. Treatment with sildenafil led to a significant improvement in systolic and diastolic LV performance. This effect was associated with less LV hypertrophy, remodeling, cardiac inflammation and apoptosis. PDE5A inhibition with sildenafil may provide a new treatment strategy for cardiac hypertrophy and adverse remodeling in the hypertensive heart.

PMID:
23117837
DOI:
10.1007/s00395-012-0308-y
[Indexed for MEDLINE]

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