Document Detail

Chronic hypoxia- and monocrotaline-induced elevation of hypoxia-inducible factor-1 alpha levels and pulmonary hypertension.
MedLine Citation:
PMID:  15067214     Owner:  NLM     Status:  MEDLINE    
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.
Yih-Loong Lai; Tai Chung Law
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomedical science     Volume:  11     ISSN:  1021-7770     ISO Abbreviation:  J. Biomed. Sci.     Publication Date:    2004 May-Jun
Date Detail:
Created Date:  2004-04-06     Completed Date:  2004-12-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421567     Medline TA:  J Biomed Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  315-21     Citation Subset:  IM    
Copyright Information:
Copyright 2004 National Science Council, ROC and S. Karger AG, Basel
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
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MeSH Terms
Anoxia / metabolism*
Hydrogen-Ion Concentration
Hypertension, Pulmonary / chemically induced,  etiology*,  metabolism
Hypoxia-Inducible Factor 1, alpha Subunit
Monocrotaline / pharmacology*
Rats, Wistar
Transcription Factors / metabolism*
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Transcription Factors; 315-22-0/Monocrotaline

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