Concentration-dependent effects of bradykinin on leukocyte recruitment and venular hemodynamics in rat mesentery.
The results of several recent studies indicate that bradykinin protects tissues against the deleterious effects of ischemia-reperfusion (I/R). However, other studies indicate that bradykinin can act as a proinflammatory agent, inducing P-selectin expression, the formation of chemotactic stimuli, and endothelial barrier disruption. In the present study, we used intravital microscopic techniques to examine the dose-dependent effects of bradykinin on leukocyte-endothelial cell interactions, the formation of platelet-leukocyte aggregates, and venular hemodynamics in rat mesentery in an attempt to explain these divergent findings. Superfusion of the mesentery with low concentrations of bradykinin (</=10(-7) M) increased venular erythrocyte velocity (V(RBC)) without increasing the number of adherent leukocytes, whereas higher concentrations (>/=10(-6) M) decreased V(RBC), increased the number of platelet-leukocyte aggregates, and induced leukocyte adhesion in single postcapillary venules. The formation of platelet-leukocyte aggregates and increased leukocyte adhesion induced by high-dose bradykinin were attenuated by administration of a B(2)-receptor (HOE-140) or a platelet-activating factor (PAF, WEB-2086) antagonist. Thus these adhesive interactions induced by high-dose bradykinin appear to be mediated by a mechanism that is dependent on B(2)-receptor activation and the formation of PAF or PAF-like lipids. The effects of bradykinin on venular V(RBC) and blood flow were also concentration dependent, with low doses producing nitric oxide-mediated vasodilation, whereas high doses decreased V(RBC) by a mechanism that is PAF independent.
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, Louisiana 71130, USA.
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Shigematsu
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Ishida
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Gute
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RJ
Korthuis
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology; D014699:Venules
D001381:Azepines; D065168:Bradykinin Receptor Antagonists; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; C065679:icatibant; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester