Efficacy of aminaftone in a rat model of monocrotaline-induced pulmonary hypertension

Vanessa Zambelli, Alessandro Santaniello, Francesca Fumagalli, Serge Masson, Raffaella Scorza, Lorenzo Beretta, Roberto Latini

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary hypertension is characterized by increased vascular resistances, that could lead to right heart failure and death. Endothelin-1 (ET-1) is a peptide with strong vasoconstrictive and pro-fibrotic properties and is one of the main mediators of pulmonary hypertension. Aminaftone, 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. The aim of this study was to test whether the inhibition of ET-1 production by aminaftone attenuates the effects of pulmonary hypertension. Pulmonary hypertension was induced through s.c. injection of 60 mg/kg monocrotaline. The rats were randomly assigned to the following experimental groups: Control; Monocrotaline; Aminaftone 30 mg/kg/day; Aminaftone 150 mg/kg/day. After 5 weeks, mortality was significantly lower in the animals treated with aminaftone at both doses compared to monocrotaline alone. Aminaftone reduced plasma concentration of ET-1 and seemed to reduce right heart hypertrophy and the wall thickness of the pulmonary arteries at the highest dose. Aminaftone may represent a novel treatment strategy of pulmonary hypertension.

Original languageEnglish
Pages (from-to)287-291
Number of pages5
JournalEuropean Journal of Pharmacology
Volume667
Issue number1-3
DOIs
Publication statusPublished - Sep 30 2011

Keywords

  • Aminaftone
  • Endothelin-1
  • Monocrotaline
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pharmacology

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