Change of level and expression of endothelin-1 in the lungs of rats with hypoxic pulmonary hypertension.

OBJECTIVE: To determine whether mRNA for endothelin-1 was present and changed in the lungs of rats exposed to chronic hypoxia. METHODS: cRNA probes for rat ET-1 and c-fos were labelled by in vitro transcription with digoxigenin-UTP for in situ hybridization. Endothelin-1 like immunoreactivity (ET-1-LI) in plasma as well as in lung homogenate was measured by radioimmunoassay. RESULTS: The vascular endothelial cells of pulmonary arteries and the bronchiolar epithelial cells were strongly positive for the ET-1 probe. The perivascular and peribronchiolar smooth muscle were positive for the c-fos probe, primarily. There was little expression of ET-1 and c-fos in the rat lungs in controls. There was significant increase of ET-1-LI levels in rats exposed to hypoxia for 3 weeks, the concentration ET-1-LI in venous samples was 3.85 +/- 1.52 ng/L (P < 0.05 as compared with the control groups), in arterial sample was 4.72 +/- 1.66 ng/L (P < 0.05) and in lung was 2.06 +/- 0.68 ng/g wet lung weight (P < 0.05). CONCLUSIONS: Chronic hypoxia elevated the mean pulmonary arterial pressure, caused vessel remodelling and the right ventricular hypertrophy. These changes were accompanied by an increase of ET-1 in plasma and lung homogenate. The expression and production of ET-1 were localized to endothelium and airway epithelium in the lungs.