Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo.
Basic Res Cardiol
; 107(6): 308, 2012 Nov.
Article
in En
| MEDLINE
| ID: mdl-23117837
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 ß +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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Piperazines
/
Sulfones
/
Ventricular Function, Left
/
Ventricular Remodeling
/
Phosphodiesterase 5 Inhibitors
/
Heart Failure
Limits:
Animals
Language:
En
Journal:
Basic Res Cardiol
Year:
2012
Type:
Article
Affiliation country:
Germany