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Coronary vasodilatation induced by endotoxin in the rabbit isolated perfused heart is nitric oxide‐dependent and inhibited by dexamethasone
Author(s) -
Smith Russell E.A.,
Palmer Richard M.J.,
Moncada Salvador
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12375.x
Subject(s) - vasoconstriction , omega n methylarginine , nitric oxide synthase , nitric oxide , vasodilation , dexamethasone , medicine , nitroarginine , endocrinology , lipopolysaccharide , chemistry , pharmacology
The coronary vasoconstriction induced by the thromboxane mimetic U46619 (9, 11 dideoxy methanoepoxy 9α, 11α prostaglandin F 2α , 3–30 n m ) was significantly attenuated in hearts obtained from rabbits treated with endotoxin (lipopolysaccharide, LPS, 200 μg 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, N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA) and N‐iminoethyl‐ l ‐ornithine ( l ‐NIO) (1–100 μ m 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.