title: Effect of all-trans-retinoic acid on the development of chronic hypoxia-induced pulmonary hypertension.
abstract: BACKGROUND
  An earlier study showed that all-trans-retinoic acid (ATRA) prevents the development of monocrotalin-induced pulmonary hypertension (PH). The purpose of the present study was to determine the effect of ATRA on another model of chronic hypoxia-induced PH.
  
  
  RESULTS
  Male Sprague-Dawley rats were given 30 mg/kg ATRA or vehicle only by gavage once daily for 14 days during hypobaric hypoxic exposure. Chronic hypoxic exposure induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes. Quantitative morphometry of the pulmonary arteries showed that ATRA treatment significantly reduced the percentage of muscularized arteries in peripheral pulmonary arteries only with an external diameter between 15 and 50 microm. ATRA treatment also significantly reduced the medial wall thickness in small muscular arteries only with an external diameter between 50 and 100 microm. Unfortunately, these reductions did not accompany the lowering of pulmonary artery pressure nor decrease in RVH. Chronic hypoxia-induced PH rats with ATRA had a loss in body weight. Chronic hypoxia increased the expression of endothelial nitric oxide synthase in the lung on western blotting and immunohistochemistry, in which ATRA treatment had no effect.
  
  
  CONCLUSIONS
  The administration of ATRA might not have a therapeutic role in preventing the development of chronic hypoxia-induced PH, because of body weight loss and the subtle preventable effects of vascular changes.
authors.affiliation: Anesthesiology and Critical Care Medicine, Physiology, Pediatrics, Mie University School of Medicine, Tsu and Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Japan.
authors.forename: Erquan
authors.initials: E
authors.lastname: Zhang
authors.forename: Baohua
authors.initials: B
authors.lastname: Jiang
authors.forename: Ayumu
authors.initials: A
authors.lastname: Yokochi
authors.forename: Junko
authors.initials: J
authors.lastname: Maruyama
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Mitani
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D001835:Body Weight; D002908:Chronic Disease; D006976:Hypertension, Pulmonary / Q000209:etiology*; D017380:Hypertrophy, Right Ventricular; D000860:Hypoxia / Q000150:complications*; D008168:Lung / Q000201:enzymology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D015431:Weight Loss
chemical_list: D014212:Tretinoin; D052250:Nitric Oxide Synthase Type III