Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA.
Nitric oxide (NO) may mediate the hypotension of septic shock, but the effect of endotoxin on inducible NO synthase (iNOS) mRNA expression remains unclear. We studied the effects of lipopolysaccharide (LPS) treatment in vivo on iNOS mRNA expression using reverse transcription and polymerase chain reaction. The iNOS mRNA was absent or negligible in any tissue studied from control rats, but was markedly increased in lung, liver, spleen, skeletal muscle and kidney from LPS-treated rats. The LPS-induced increase in iNOS mRNA was prevented by dexamethasone. Our results indicate that LPS treatment in vivo induces the expression of an iNOS mRNA via a dexamethasone-sensitive mechanism, and thus provide direct molecular evidence for the involvement of NO in septic shock.
Liu
S
S
Department of Thoracic Medicine, National Heart & Lung Institute, London, U.K.
Adcock
I M
IM
Old
R W
RW
Barnes
P J
PJ
Evans
T W
TW
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase; D016376:Oligonucleotides, Antisense; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012477:Salmonella enteritidis; D013154:Spleen / Q000187:drug effects / Q000201:enzymology
D017931:DNA Primers; D004731:Endotoxins; D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000594:Amino Acid Oxidoreductases