Methylprednisolone inhibits endotoxin-induced depression of contractile function in human arteries in vitro.
We have studied the effect of methylprednisolone on endotoxin-induced depression of contractile function in human gastroepiploic arteries. Endotoxin diminished the contractile response to noradrenaline in both the presence and absence of endothelium. This attenuation began after 4 h and reached a maximum after 10 h of endotoxin exposure. The cGMP content of endotoxin-treated rings was approximately seven-fold higher than in control rings. These endotoxin-mediated responses were blocked by L-NAME and methylene blue. These data indicate that the main cause of vascular hyposensitivity to noradrenaline was massive generation of nitric oxide. Pretreatment with methyl-prednisolone at concentrations (2.0-20.0 micrograms ml-1) similar to those achieved in plasma after therapeutic administration dose-dependently inhibited these endotoxin-mediated responses. These data support the concept that pharmacological administration of methylprednisolone has the potential to prevent endotoxin-induced depression of the contractile response to noradrenaline seen in endotoxaemic shock.
Tsuneyoshi
I
I
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, Japan.
Kanmura
Y
Y
Yoshimura
N
N
D000109:Acetylcholine / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003251:Constriction, Pathologic / Q000517:prevention & control; D046508:Culture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008775:Methylprednisolone / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D009852:Omentum / Q000098:blood supply*
D004731:Endotoxins; D005938:Glucocorticoids; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine; D008775:Methylprednisolone