Attenuation of endotoxin-induced increase in glucose metabolism by platelet-activating factor antagonist.
Platelet-activating factor (PAF) has recently been proposed as a putative mediator of various pathophysiologic events during endotoxemia. The aim of the present study was to determine the relative importance of PAF in producing the alterations in carbohydrate metabolism following endotoxin. Chronically catheterized conscious rats were treated with SRI 63-441, a specific PAF receptor antagonist, or saline prior to Escherichia coli endotoxin (100 micrograms/100 g body weight, LD10) administration. Hemodynamic and whole-body glucose kinetic changes, the latter assessed by a constant intravenous infusion of [6-3H] glucose, were determined throughout the 4-hr experimental protocol. Endotoxin induced a transient 30-35% reduction in mean arterial blood pressure (MABP) in animals treated with saline. The PAF-antagonist attenuated this hypotensive effect, and MABP was only reduced by 14-18%. Endotoxin increased plasma glucose and lactate levels, as well as the rate of glucose appearance (Ra) in saline-treated rats. The PAF antagonist reduced the hyperglycemia by 60-75% and tended to prevent the hyperlactacidemia. The endotoxin-induced elevation in glucose Ra was also attenuated by 55%. A similar degree of hyperglucagonemia was observed following endotoxin in both groups, and plasma insulin concentrations were not different. However, plasma catecholamine levels were significantly lower (30-70%) in endotoxemic rats treated with the PAF antagonist. These results suggest that the enhanced production of PAF following endotoxin may be responsible, at least in part, for the early hemodynamic changes. The role of PAF as a mediator of endotoxin-induced glucose dyshomeostasis, however, may be secondary to its hemodynamic effects.
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
C H
CH
Lang
C
C
Dobrescu
D M
DM
Hargrove
G J
GJ
Bagby
J J
JJ
Spitzer
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011806:Quinolinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D006728:Hormones; D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; C050531:SRI 63-441; D005947:Glucose