Platelet activating factor receptor antagonist improves survival and attenuates eicosanoid release in severe endotoxemia.
Exogenous platelet activating factor (PAF) causes hypotension, plasma extravasation, metabolic acidosis, and death. These effects are similar to those of endotoxin as well as the eicosanoids. A specific PAF receptor antagonist, BN52021, was used to determine its effects on the hemodynamic events, the eicosanoid production, and on survival in severe rat endotoxemia. Endotoxin alone significantly produced hypotension, prostaglandins (TxB2, PGE2) release, and death. In contrast pretreatment with BN52021, a specific PAF receptor antagonist, significantly altered the hypotension, significantly attenuated the eicosanoid release, and improved the survival rate (p less than 0.01). These findings suggest that PAF receptor activation is an early event in endotoxemia. Eicosanoid release in endotoxemia could be related to PAF synthesis and PAF receptor activation. These findings support the hypothesis that there may be an intimate relationship between PAF and the eicosanoids and that in endotoxemia some of the effects of PAF may be mediated via the cyclo-oxygenase pathway.
Fletcher
J R
JR
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
DiSimone
A G
AG
Earnest
M A
MA
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis*; D004224:Diterpenes; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D046934:Ginkgolides; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D010936:Plant Extracts; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000188:drug therapy*; D013929:Thromboxane B2 / Q000096:biosynthesis*
D004224:Diterpenes; D004731:Endotoxins; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D013929:Thromboxane B2; C044101:endotoxin, Escherichia coli; C045856:ginkgolide B; D015232:Dinoprostone