Concentration-dependent effects of bradykinin on leukocyte recruitment and venular hemodynamics in rat mesentery

Concentration-dependent effects of bradykinin on leukocyte recruitment and venular hemodynamics... Abstract 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. leukocyte adhesion postcapillary venules erythrocyte velocity B 2 receptors platelet-activating factor nitric oxide synthase cyclooxygenase Footnotes Address for reprint requests and other correspondence: R. J. Korthuis, Dept. of Molecular and Cellular Physiology, LSU Medical Center, 1501 Kings Highway, Shreveport, LA 71130 (E-mail: rkorth@lsumc.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1999 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

Concentration-dependent effects of bradykinin on leukocyte recruitment and venular hemodynamics in rat mesentery

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
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Abstract

Abstract 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. leukocyte adhesion postcapillary venules erythrocyte velocity B 2 receptors platelet-activating factor nitric oxide synthase cyclooxygenase Footnotes Address for reprint requests and other correspondence: R. J. Korthuis, Dept. of Molecular and Cellular Physiology, LSU Medical Center, 1501 Kings Highway, Shreveport, LA 71130 (E-mail: rkorth@lsumc.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. §1734 solely to indicate this fact. Copyright © 1999 the American Physiological Society

Journal

AJP - Heart and Circulatory PhysiologyThe American Physiological Society

Published: Jul 1, 1999

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