Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway.
J Cardiovasc Pharmacol
; 44(5): 596-600, 2004 Nov.
Article
en En
| MEDLINE
| ID: mdl-15505498
ABSTRACT
In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
/
GMP Cíclico
/
Péptidos Natriuréticos
/
Insuficiencia Cardíaca
/
Hipertensión Pulmonar
Tipo de estudio:
Prognostic_studies
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón