HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/H2306    most recent 00601.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Ishikawa, M. Articles by Minamitani, H. Search for Related Content PubMed PubMed Citation Articles by Ishikawa, M. Articles by Minamitani, H.

Angiotensin II type 1 receptor signaling contributes to platelet-leukocyte-endothelial cell interactions in the cerebral microvasculature

Departments of ¹Neurosurgery and ²Internal Medicine, National Hospital Organization Saitama Hospital, Wako-city, Japan; ³Department of Neurosurgery, Saitama City Hospital, Saitama City, Japan; ⁴Graduate School of Science and Technology, Keio University, Yokohama, Japan; and ⁵Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana

Submitted 8 June 2006 ; accepted in final form 20 December 2006

Angiotensin II type 1 (AT₁) receptor signaling has been implicated in cerebral microvascular alterations associated with ischemia, diabetes mellitus, hypercholesterolemia, and atherosclerosis. Platelets, which express AT₁ receptors, also appear to contribute to the thrombogenic and inflammatory responses that are elicited by these pathological conditions. This study assesses the role of AT₁ receptor activation on platelet-leukocyte-endothelial cell interactions elicited in cerebral microvasculature by ischemia and reperfusion. Intravital microscopy was used to monitor the adhesion of platelets and leukocytes that were labeled with different fluorochromes, whereas dihydrorhodamine-123 was used to quantify oxygen radical production in cerebral surface of mice that were either treated with the AT₁ receptor agonist Val-angiotensin II (ANG II) or subjected to bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. ANG II elicited a dose- and time- dependent increase in platelet-leukocyte-endothelial cell interactions in cerebral venules that included rolling platelets, adherent platelets on the leukocytes and the endothelial cells, rolling leukocytes, and adherent leukocytes. All of these interactions were attenuated by treatment with either P-selectin or P-selectin glycoprotein ligand 1 (PSGL-1) antibody. The AT₁ receptor antagonist candesartan and losartan as well as diphenyleneiodonium, an inhibitor of flavoproteins including NAD(P)H oxidase, significantly reduced the platelet-leukocyte-endothelial cell interactions elicited by either ANG II administration or BCCAO/reperfusion. The increased oxygen radical generation elicited by BCCAO/reperfusion was also attenuated by candesartan. These findings are consistent with an AT₁ receptor signaling mechanism, which involves oxygen radical production and ultimately results in P-selectin- and PSGL-1-mediated platelet-leukocyte-endothelial cell interactions in the cerebral microcirculation

P-selectin; cerebral ischemia; reactive oxygen species; reduced nicotinamide adenine dinucleotide phosphate oxidase

This article has been cited by other articles:

				S. Chen, G. Li, W. Zhang, J. Wang, C. D. Sigmund, J. E. Olson, and Y. Chen Ischemia-induced brain damage is enhanced in human renin and angiotensinogen double-transgenic mice Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1526 - R1531. [Abstract] [Full Text] [PDF]

				S. Terao, G. Yilmaz, K. Y. Stokes, J. Russell, M. Ishikawa, T. Kawase, and D. N. Granger Blood Cell-Derived RANTES Mediates Cerebral Microvascular Dysfunction, Inflammation, and Tissue Injury After Focal Ischemia-Reperfusion Stroke, September 1, 2008; 39(9): 2560 - 2570. [Abstract] [Full Text] [PDF]

				S. Terao, G. Yilmaz, K. Y. Stokes, M. Ishikawa, T. Kawase, and D. N. Granger Inflammatory and Injury Responses to Ischemic Stroke in Obese Mice Stroke, March 1, 2008; 39(3): 943 - 950. [Abstract] [Full Text] [PDF]