Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat.
The induction by endotoxin of Ca2(+)-independent nitric oxide (NO) synthase in the lung and liver of the rat was prevented by the glucocorticoids dexamethasone and cortisol but not by progesterone. The activity of the constitutive Ca2(+)-dependent NO synthase in the brain and the aorta was not affected by treatment with either endotoxin or glucocorticoids. In the aorta a Ca2(+)-independent NO synthase was also found following endotoxin treatment of rats, and this induction was likewise prevented by dexamethasone. The Ca2(+)-dependent NO synthase in the aorta was located in the vascular endothelium, whereas the Ca2(+)-independent enzyme was predominantly located in the vascular smooth muscle layer. Inhibition of induction of the Ca2(+)-independent NO synthase in vivo may underlie some of the physiological and pharmacological effects of the anti-inflammatory glucocorticoids.
Wellcome Research Laboratories, Beckenham, Kent, U.K.
R G
RG
Knowles
M
M
Salter
S L
SL
Brooks
S
S
Moncada
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019001:Nitric Oxide Synthase; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D005938:Glucocorticoids; D011374:Progesterone; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006854:Hydrocortisone