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.
Junbao
D
D
First Hospital of Beijing Medical University, PR China.
Jianfeng
J
J
Wanzhen
L
L
Bin
Z
Z
Heping
Z
Z
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002908:Chronic Disease; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D017403:In Situ Hybridization; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester