Chronic hypoxia- and monocrotaline-induced elevation of hypoxia-inducible factor-1 alpha levels and pulmonary hypertension.
A close relationship exists between hypoxia-inducible factor (HIF)-1alpha and pulmonary hypertension. The present study was carried out to explore if there are temporal alterations in HIF-1alpha levels during prolonged hypoxia and after monocrotaline (MCT) treatment. First, young Wistar rats were divided into 5 groups: control, hypoxia-1, hypoxia-2, hypoxia-3 and hypoxia-4. Hypoxic rats were placed in a closed hypobaric chamber (380 mm Hg) for a 1-week (hypoxia-1), 2-week (hypoxia-2), 3-week (hypoxia-3) or 5-week (hypoxia-4) period. Second, other young Wistar rats were divided into 4 groups: control, MCT-1, MCT-2 and MCT-3. MCT-treated rats were injected subcutaneously once with MCT (60 mg/kg) for a 1-week (MCT-1), 2-week (MCT-2) or 3-week (MCT-3) period. Subsequently, pulmonary arterial pressure (Ppa) and the weight ratio of the right ventricle to the left ventricle plus the septum [RV/(LV + S)] were measured, and lungs were obtained for the determination of HIF-1alpha via Western blot analysis. Both hypoxia and MCT induced temporal increases in the Ppa, the ratio RV/(LV + S) and HIF-1alpha levels. A close relationship between the Ppa and HIF-1alpha level was found in both hypoxia- and MCT-treated animals. In addition, the PaO(2) level significantly decreased in rats 1-3 weeks after MCT treatment. These results, along with previous data in the literature, suggest that both chronic hypoxia- and MCT-induced lung hypoxia activate an increase in the production of HIF-1alpha, and result in vascular remodeling and pulmonary hypertension.
Lai
Yih-Loong
YL
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. tiger@ha.mc.ntu.edu.tw
Law
Tai Chung
TC
D000818:Animals; D006863:Hydrogen-Ion Concentration; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016686:Monocrotaline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D016686:Monocrotaline