Inhibitory effects of dexamethasone in endotoxic shock and its relation to PAF-acether synthesis in the gastrointestinal tract and lung.
Endotoxic shock is accompanied by significant increases in PAF-acether synthesis, particularly by the lung. The onset of tissue damage and increases in vascular permeability in the gastrointestinal tract correlate temporally with the changes in PAF-acether synthesis and have previously been shown to be inhibited by PAF-acether antagonists. In the present study, the effects of pretreatment with dexamethasone on endotoxin-induced hemoconcentration and hypotension were examined in the rat. Furthermore, the effects of dexamethasone on PAF-acether synthesis and gastrointestinal vascular permeability following administration of endotoxin were also studied. Pretreatment with dexamethasone resulted in a significant attenuation of endotoxin-induced hemoconcentration, hypotension and damage in the duodenum and stomach. Dexamethasone also significantly reduced PAF-acether synthesis by the lung. However, dexamethasone pretreatment had no significant effect on endotoxin-induced increases in PAF-acether release and vascular permeability in the gastrointestinal tissues. The mechanism of the protective actions of dexamethasone may be related to inhibition of the release of PAF-acether from the lung. PAF released from gastrointestinal tissues likely contributes little to the systemic disturbances in endotoxic shock.
Ibbotson
G C
GC
Department of Physiology, Queen's University, Kingston, Ont., Canada.
Wallace
J L
JL
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004064:Digestive System / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
D010972:Platelet Activating Factor; D003907:Dexamethasone