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ANGIOTENSIN II MEDIATES POSTISCHEMIC LEUKOCYTE‐ENDOTHELIAL INTERACTIONS: ROLE OF CHYMASE AND ACE, AT 1 and AT 2 RECEPTORS, CGRP, AND NADPH OXIDASE
Author(s) -
Yusof Mozow,
Kamada Kazuhiro,
Gaskin F Spencer,
Korthuis Ronald J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1236-a
Subject(s) - nadph oxidase , apocynin , angiotensin ii receptor type 1 , angiotensin ii , receptor , chemistry , renin–angiotensin system , chymase , pharmacology , endocrinology , medicine , losartan , biochemistry , enzyme , oxidative stress , blood pressure
Vascular inflammation and enhanced production of angiotensin II (Ang II) are involved in the pathogenesis of hypertension and diabetes, disease states that predispose the afflicted individuals to ischemic disorders. Therefore, we postulated that Ang II may play a role promoting leukocyte rolling (LR) and adhesion (LA) in postcapillary venules after exposure of the small intestine to ischemia/reperfusion (I/R). Using an intravital microscopic approach in C57BL/6J mice, we show that Ang II AT 1 or AT 2 receptor antagonism (with valsartan or PD123,319, respectively), inhibition of ACE (captopril), or CGRP receptor blockade (CGRP8‐37) prevents postischemic LR but does not influence I/R‐induced LA. However, both postischemic LR and LA are greatly abolished by concomitant AT 1 and AT 2 receptor blockade or chymase inhibition (with Y‐40079). Additionally, exogenously administered Ang II increases LR and LA, effects that are attenuated by pretreatment with a CGRP8‐37 or apocynin, a NADPH oxidase inhibitor. Our work suggests that Ang II plays an important role in inducing LR and LA, through the engagement of both AT 1 and AT 2 receptors and may be mediated by CGRP and NADPH oxidase.