Normobaric hypoxia stimulates endothelin-1 gene expression in the rat
Elton, T.S.; Oparil, S.; Taylor, G.R.; Hicks, P.H.; Yang, R.H.; Jin, H.; Chen, Y.F.
American Journal of Physiology 263(6 Pt 2): R1260-R1264
1992
ISSN/ISBN: 0002-9513 PMID: 1481936 Document Number: 402718
The current study tested the hypothesis that exposure to hypoxia enhances endothelin-1 (ET-1) gene expression and elevates circulating ET-1 levels in the rat. Rats were exposed to normobaric hypoxia (10% O-2) or room air for 24 or 48 h. ET-1 in arterial blood was measured by radioimmunoassay. ET-1 gene transcript levels were measured by the slot blot technique on total RNA isolated from lung, right and left atria, right and left ventricles, kidney, spleen, liver, brain, main trunk of pulmonary artery, and thoracic aorta. Blots were probed with a 0.5 kb rat prepro ET-1 cDNA that does not cross-hybridize with mRNA from ET-2 or ET-3. Plasma ET-1 levels were increased significantly at 24 (10.03 +- 2.33 pg/ml) and 48 h (14.02 +- 3.44 pg/ml) of hypoxia compared with air controls (4.14 lt 0.66 pg/ml). ET-1 mRNA levels were increased significantly (2-fold) in lung and right atrium after 48h or hypoxia; no change were seen in organs perfused by the systemic vascular bed. These findings suggest that the hypoxia-induced increase in circulating ET-1 levels is mainly of pulmononary origin. A paracrine effect of ET-1 produced by lung endothelial cells could account for hypoxic pulmonary hypertension.