Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock.
The relationship between vascular tone and the induction by endotoxin of a nitric oxide (NO) synthase was studied in vitro in rings of rat thoracic aorta. In rings with and without endothelium there was a time-dependent induction of NO synthase accompanied by both spontaneous and L-arginine-induced relaxation and by reduced contractility to phenylephrine. These effects, which were attributable to the presence of endotoxin in the Krebs' buffer, were attenuated by cycloheximide, polymyxin B and inhibitors of NO synthase. Furthermore, dexamethasone inhibited the induction of NO synthase and the consequent effects on vascular tone. These findings indicate that prevention of the induction of NO synthase by glucocorticoids may be an important component of their therapeutic action.
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
D D
DD
Rees
S
S
Cellek
R M
RM
Palmer
S
S
Moncada
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000201:enzymology; D004731:Endotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000627:therapeutic use; D009129:Muscle Tonus / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D012772:Shock, Septic / Q000188:drug therapy / Q000201:enzymology*
D004731:Endotoxins; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D003907:Dexamethasone; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D011112:Polymyxin B; D002118:Calcium