Chronic hypoxia- and monocrotaline-induced elevation of hypoxia-inducible factor-1 alpha levels and pulmonary hypertension.

Abstract

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.

• Authors: Yih-Loong Lai, Tai Chung Law
• Journal: Journal of biomedical science (J Biomed Sci) 2004 May-Jun Vol. 11 Issue 3 Pg. 315-21 ISSN: 1021-7770 [Print] England
• PMID: 15067214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• Transcription Factors
• Monocrotaline

Topics

• Animals
• Hydrogen-Ion Concentration
• Hypertension, Pulmonary (chemically induced, etiology, metabolism)
• Hypoxia (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit
• Monocrotaline (pharmacology)
• Rats
• Rats, Wistar
• Transcription Factors (metabolism)