Platelet activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone.
Evidence from three types of experiments indicates that platelet activating factor (PAF)1 is an important mediator of endotoxin-induced hypotension in rats. a) Endotoxin infusion stimulates the time-dependent appearance of PAF in the blood. b) PAF infusion results immediately (less than 30 sec) in hypotension while endotoxin-induced hypotension takes 3-5 min to occur, allowing time for PAF production. c) Infusion of the specific PAF-receptor antagonist kadsurenone (2.2 mumole/kg bolus, 0.9 mumoles/min/kg continuous infusion), which inhibits PAF-induced hypotension by 67%, causes a 67% reversal of endotoxin-elicited hypotension. An additional finding of this study is that rats respond hypotensively to each of a series of low-dose PAF infusions but only to the first low-dose endotoxin infusion. These endotoxin-refractory rats do respond to subsequent PAF infusions.
Doebber
T W
TW
Wu
M S
MS
Robbins
J C
JC
Choy
B M
BM
Chang
M N
MN
Shen
T Y
TY
D000818:Animals; D001572:Benzofurans; D001578:Benzopyrans / Q000494:pharmacology*; D004731:Endotoxins; D004926:Escherichia coli; D005260:Female; D007022:Hypotension / Q000139:chemically induced*; D007700:Kinetics; D017705:Lignans; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled
D001572:Benzofurans; D001578:Benzopyrans; D004731:Endotoxins; D017705:Lignans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C044540:kadsurenone