Tissue expression of endothelin-1 mRNA in endotoxaemia.
Circulating endothelin-1 concentrations are elevated in animal models of sepsis. The major actions of endothelin-1 appear to be as a local autocrine and paracrine factor, rather than as a circulating hormone, and plasma concentrations may not reflect local tissue concentrations. We therefore measured tissue expression of mRNA encoding pre-pro-endothelin-1 by RNase protection assays, as an indicator of local production of ET-1 in an in vivo rat model of endotoxaemia. The effects of dexamethasone pre-treatment were also examined. There was a tissue-specific increase in pre-pro-endothelin-1 mRNA in endotoxaemia, apparent at 6h after endotoxin challenge in heart and lung. No significant changes in expression were seen in kidney or skeletal muscle. Dexamethasone pre-treatment significantly attenuated the rise in pre-pro-endothelin-1 mRNA in heart at 6h. Therefore, we have demonstrated tissue-specific differences in the effect of endotoxin upon pre-pro-endothelin-1 mRNA expression and in sensitivity to dexamethasone. This could account for some of the inter-tissue differences seen in local vascular response to endotoxin.
Kaddoura
S
S
National Heart and Lung Institute, Imperial College, London, Royal Brompton Hospital, England, United Kingdom.
Curzen
N P
NP
Evans
T W
TW
Firth
J D
JD
Poole-Wilson
P A
PA
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D016232:Endothelins / Q000235:genetics*; D004731:Endotoxins / Q000097:blood*; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium; D014018:Tissue Distribution
D016232:Endothelins; D004731:Endotoxins; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003907:Dexamethasone