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(Circulation. 2000;102:2118.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Angiotensin II Induces Leukocyte–Endothelial Cell Interactions In Vivo Via AT₁ and AT₂ Receptor–Mediated P-Selectin Upregulation

Laura Piqueras; Paul Kubes, PhD; Angeles Alvarez; Enrique O’Connor, PhD; Andrew C. Issekutz, MD; Juan V. Esplugues, MD, PhD; Maria-Jesus Sanz, PhD

From the Departments of Pharmacology (L.P., A.A., J.V.E., M.-J.S.) and Biochemistry (E.O.), University of Valencia, Spain; the Immunology Research Group, University of Calgary, Canada (P.K.); and Departments of Pediatrics, Pathology, Microbiology, and Immunology, Dalhousie University, Halifax, Canada (A.C.I.).

Background—Angiotensin II (Ang II) plays a critical role in the development of vascular lesions in hypertension, atherosclerosis, and several renal diseases. Because Ang II may contribute to the leukocyte recruitment associated with these pathological states, the aim of the present study was to assess the role of Ang II in leukocyte–endothelial cell interactions in vivo.

Methods and Results—Intravital microscopy of the rat mesenteric postcapillary venules was used. Sixty minutes of superfusion with 1 nmol/L Ang II induced a significant increase in leukocyte rolling flux (83.8±20.7 versus 16.4±3.1 cells/min), adhesion (11.4±1.0 versus 0.8±0.5 cells/100 µm), and emigration (4.0±0.7 versus 0.2±0.2 cells/field) without any vasoconstrictor activity. These effects were not mediated by mast cell activation. Intravenous pretreatment with AT₁ (losartan) or AT₂ (PD123,319) receptor antagonists significantly reduced Ang II–induced responses. A combination of both receptor antagonists inhibited the leukocyte rolling flux, adhesion, and extravasation elicited by Ang II at 60 minutes. Pretreatment of animals with fucoidin or an adhesion-blocking anti–rat P-selectin monoclonal antibody abolished Ang II–induced leukocyte responses. Furthermore, rat platelet P-selectin expression was not affected by Ang II stimulation.

Conclusions—Ang II induces significant leukocyte rolling, adhesion, and emigration, which may contribute not only to hypertension but also to the onset and progression of the vascular damage associated with disease states in which plasma levels of this peptide are elevated.

Key Words: angiotensin • endothelium • leukocytes • cell adhesion molecules • glycoproteins

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