Influence of the platelet-activating factor receptor antagonist BN52021 on endotoxin-induced leukocyte adherence in rat mesenteric venules.
The aim of this study was to investigate the influence of the platelet-activating factor (PAF) antagonist BN52021 on endotoxin-induced leukocyte-endothelium interactions and on venular microcirculation. The rates of leukocyte adherence and changes in red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate were monitored in rat mesenteric venules following intravenous lipopolysaccharide (LPS) exposure (15 mg/kg body wt). The experiments were performed in LPS-treated control animals and in animals pretreated with the PAF receptor antagonist BN52021. LPS exposure induced a marked increase in adherent leukocytes in the control group compared to the BN52021-pretreated group. Thirty minutes after LPS injection, 6.1 +/- 0.8 leukocytes were adherent to 100 microns of venule in the control group compared to 2.5 +/- 0.5 in BN52021-pretreated animals (P < 0.01). The increased leukocyte adherence in the control group was accompanied by leukocytopenia. Red cell velocity, volumetric blood flow, vessel diameter, and venular shear rate did not differ between groups, indicating that increased leukocyte adherence in the control group was not due to diminished hydrodynamic dispersal forces. The attenuation of leukocyte adherence by the PAF receptor antagonist BN52021 suggests that PAF is involved in the mediation of the initial process of leukocyte sticking to the endothelium after LPS stimulation.
Schmidt
H
H
Department of Anesthesiology, University of Heidelberg, Germany.
Ebeling
D
D
Bauer
H
H
Bŏhrer
H
H
Gebhard
M M
MM
Martin
E
E
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004224:Diterpenes; D004731:Endotoxins / Q000494:pharmacology; D046934:Ginkgolides; D006439:Hemodynamics; D007783:Lactones / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013152:Splanchnic Circulation; D014699:Venules / Q000502:physiology
D004224:Diterpenes; D004731:Endotoxins; D046934:Ginkgolides; D007783:Lactones; D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B