I. Tsuneyoshi et al., METHYLPREDNISOLONE INHIBITS ENDOTOXIN-INDUCED DEPRESSION OF CONTRACTILE FUNCTION IN HUMAN ARTERIES IN-VITRO, British Journal of Anaesthesia, 76(2), 1996, pp. 251-257
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.