Coronary vasodilatation induced by endotoxin in the rabbit isolated perfused heart is nitric oxide-dependent and inhibited by dexamethasone.
The coronary vasoconstriction induced by the thromboxane mimetic U46619 (9, 11 dideoxy methanoepoxy 9 alpha, 11 alpha prostaglandin F2 alpha, 3-30 nM) was significantly attenuated in hearts obtained from rabbits treated with endotoxin (lipopolysaccharide, LPS, 200 micrograms kg-1, i.v.) 4 h before isolation of the heart. Under these conditions the vasoconstriction induced by two inhibitors of nitric oxide (NO) synthase, NG-monomethyl-L-arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO) (1-100 microM for each) was significantly enhanced when compared to that induced in hearts from control animals. Both the decreased response to U46619 and the increased response to inhibitors of NO synthase were significantly attenuated by administration of dexamethasone (4 mg kg-1, i.v.) 90 min before treatment with LPS. These data are consistent with the induction, by LPS, of an NO synthase, and the inhibition of this induction by dexamethasone. The enhanced NO synthesis contributes to the haemodynamic changes known to occur in endotoxin shock.
Smith
R E
RE
Wellcome Research Laboratories, Beckenham, Kent.
Palmer
R M
RM
Moncada
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D004731:Endotoxins; D008070:Lipopolysaccharides; D011450:Prostaglandin Endoperoxides, Synthetic; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003907:Dexamethasone; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases