title: Efficacy of aminaftone in a rat model of monocrotaline-induced pulmonary hypertension.
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.
authors.affiliation: Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milano (MI), Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zambelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Santaniello
authors.forename: Francesca
authors.initials: F
authors.lastname: Fumagalli
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scorza
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Beretta
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
mesh_terms: D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage / Q000633:toxicity*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D062366:para-Aminobenzoates
chemical_list: D019332:Endothelin-1; D062366:para-Aminobenzoates; C016217:aminaftone; D016686:Monocrotaline; D010129:4-Aminobenzoic Acid