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 endotheli al cells or smooth muscle cells in chronically hypoxic rats by use of in si tu hybridization. Male Wistar rats (n = 40) were randomly divided into 1-we ek hypoxia group, 1-week hypoxia with L-arginine (L-arg) group, 1-week hypo xia with N-omega-nitro-L-arginine methyl ester (L-NAME) group, 2-week hypox ia group, 2-week hypoxia with L-arg group, and 2-week hypoxia with L-NAME g roup. All rats were put into a normobaric hypoxic chamber with an oxygen co ncentration of 10 +/- 0.5% for hypoxic challenge. The results showed that m ost pulmonary arteries had 1-50% of the endothelial cells showing positive signals for ET-1 expression in hypoxic rats, which was significantly suppre ssed by L-arg. L-NAME, however, significantly augmented ET-1 gene expressio n in pulmonary artery endothelial cells and smooth muscle cells. The result s 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 hypo xic pulmonary circulation.