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.