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. E ndotoxin 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 10h of endotoxin exposure. The cGMP co ntent of endotoxin-treated rings was approximately seven-fold higher t han 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 methylprednisolone at concentrations (2.0-20.0 mu g ml(-1)) similar to those achieved in plasma after thera peutic administration dose-dependently inhibited these end otoxin-medi ated responses. These data support the concept that pharmacological ad ministration of methylprednisolone has the potential to prevent endoto xin-induced depression of the contractile response to noradrenaline se en in endotoxaemic shock.