Rosiglitazone attenuates hypoxia-induced pulmonary arterial hypertension in rats.
OBJECTIVE
Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) is decreased in the lungs of patients with pulmonary hypertension, and PPARgamma ligands have been associated with the release of vasoactive substances from vascular endothelial cells and prevention of vascular remodelling. We hypothesized that PPARgamma may play a critical role in the development of pulmonary hypertension induced by chronic hypoxia.


METHODS
Male adult Sprague-Dawley rats were exposed to normoxia, normoxia and rosiglitazone (8 mg/kg orally, 5 days/week), hypoxia (12% inspired O(2) fraction), or hypoxia and rosiglitazone for 4 weeks. On the last day of the fourth week, pulmonary arterial pressure was measured and morphological changes in pulmonary vessels were assessed. The expression of PPARgamma, endothelin (ET)-1 and vascular endothelial growth factor (VEGF) was also analysed.


RESULTS
Rosiglitazone inhibited the development of pulmonary hypertension, and pulmonary vascular remodelling induced by chronic hypoxia. PPARgamma expression was decreased and expression of ET-1 and VEGF was increased in lung tissues of the hypoxia group. Rosiglitazone treatment prevented the hypoxia-induced reduction in PPARgamma expression, and restored ET-1 and VEGF expression almost to the levels of the normoxia group.


CONCLUSIONS
Rosiglitazone inhibited the development of pulmonary hypertension induced by chronic hypoxia, perhaps by reversing the changes in PPARgamma, ET-1 and VEGF expression induced by hypoxia. These findings indicate that rosiglitazone may be beneficial in the treatment of chronic hypoxic pulmonary hypertension.
Kim
Eun Kyung
EK
Department of Pulmonary and Critical Care Medicine, Bundang CHA Hospital, College of Medicine, CHA University, Seongnam, Korea.
Lee
Ji-Hyun
JH
Oh
Yeon-Mock
YM
Lee
Yun-Song
YS
Lee
Sang-Do
SD
D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000032:analysis; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D042442:Vascular Endothelial Growth Factors / Q000032:analysis
D019332:Endothelin-1; D047495:PPAR gamma; D045162:Thiazolidinediones; D042442:Vascular Endothelial Growth Factors; D000077154:Rosiglitazone