title: Pathophysiology of infantile pulmonary arterial hypertension induced by monocrotaline.
abstract: Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Al. Prof Hernâni Monteiro, 4200-319, Porto, Portugal, marina_f_neto@hotmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Dias-Neto
authors.forename: Ana
authors.initials: A
authors.lastname: Luísa-Neves
authors.forename: Sónia
authors.initials: S
authors.lastname: Pinho
authors.forename: Nádia
authors.initials: N
authors.lastname: Gonçalves
authors.forename: Maria
authors.initials: M
authors.lastname: Mendes
authors.forename: Catarina
authors.initials: C
authors.lastname: Eloy
authors.forename: José M
authors.initials: JM
authors.lastname: Lopes
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonçalves
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferreira-Pinto
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
authors.forename: Tiago
authors.initials: T
authors.lastname: Henriques-Coelho
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D019332:Endothelin-1; D011763:Pyrrolizidine Alkaloids; D012333:RNA, Messenger; D014157:Transcription Factors; D020097:Natriuretic Peptide, Brain; D016686:Monocrotaline