Abstract 15583: Evaluation of the Efficacy of Aminaftone in a Rat Model of Monocrotaline-induced Pulmonary Hypertension
Introduction: Increased vascular resistances give rise to pulmonary arterial hypertension (PAH), leading to right heart failure and death. The main mediator of PAH is endothelin-1 (ET-1), a peptide with strong vasoconstrictive and pro-fibrotic properties. Aminaftone (AMNA), a synthetic molecule derivative of 4-amynobenzoic acid, down-regulates ET-1 production in vitro by interfering with the transcription of the pre-pro-ET-1 gene.
Hypothesis: We tested whether inhibition of ET-1 production by AMNA prevented the development of PAH from its early stages.
Methods: PAH was induced trough s.c. injection of 60mg/kg MCT. The rats were randomly assigned to the following four experimental groups: 1) Control (CTR); 2) MCT; 3) MCT+Aminaftone 30 mg/kg/day (AMNA30); and 4) MCT+Aminaftone 150 mg/kg/day (AMNA 150). Rats were sacrified after 5 weeks, blood was collected and heart was dissected, weighed and stored for histological analysis.
Results: Rats treated with AMNA at both doses showed a lower mortality compared to MCT group (p<0.05). AMNA 150 group significantly attenuated hypertrophy of the right ventricule and reduced ET-1 plasma level compared to other groups (Table 1).
Conclusions: Aminaftone reduced ET-1 plasma level in a rat model of MCT-induced PAH; high dose treatment with AMNA seemed to reduce right heart hypertrophy. AMNA may represent a novel treatment strategy for PAH.
- © 2010 by American Heart Association, Inc.