Effect of all-trans-retinoic acid on the development of chronic hypoxia-induced pulmonary hypertension.
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.
Zhang
Erquan
E
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.
Jiang
Baohua
B
Yokochi
Ayumu
A
Maruyama
Junko
J
Mitani
Yoshihide
Y
Ma
Ning
N
Maruyama
Kazuo
K
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
D014212:Tretinoin; D052250:Nitric Oxide Synthase Type III