Nitric oxide impacts endothelin-1 gene expression in intrapulmonary arteries of chronically hypoxic rats

This study aimed to investigate whether nitric oxide (NO) could inhibit the elevated endothelin-1 (ET-1) gene expression by pulmonary artery endothelial cells or smooth muscle cells in chronically hypoxic rats by use of in situ hybridization. Male Wistar rats (n = 40) were randomly divided into 1-week hypoxia group, 1-week hypoxia with L-arginine (L-arg) group, 1-week hypoxia with N(omega)-nitro-L-arginine methyl ester (L-NAME) group, 2-week hypoxia group, 2-week hypoxia with L-arg group, and 2-week hypoxia with L-NAME group. All rats were put into a normobaric hypoxic chamber with an oxygen concentration of 10 +/- 0.5% for hypoxic challenge. The results showed that most pulmonary arteries had 1-50% of the endothelial cells showing positive signals for ET-1 expression in hypoxic rats, which was significantly suppressed by L-arg. L-NAME, however, significantly augmented ET-1 gene expression in pulmonary artery endothelial cells and smooth muscle cells. The results suggest that endogenous NO markedly inhibits ET-1 mRNA expression in both pulmonary artery endothelial cells and smooth muscle cells in chronically hypoxic rats, which may be one of the mechanisms by which NO modulates hypoxic pulmonary circulation.