Title

The Role of NADPH Oxidase Isoform 1 (NOX1) in L-NAME-Induced Leukocyte-Endothelial Interactions in Rat Mesenteric Postcapillary Venules

Document Type

Article

Publication Date

2016

Abstract

Vascular endothelial dysfunction and subsequent inflammation underlie many pathological diseases such as cardiovascular disease, diabetes, and hypertension. Both events are principally initiated by reduced endothelial-derived nitric oxide (NO) bioavailability and/or activation of vascular/leukocyte NADPH oxidase. NADPH oxidase has 7 isoforms (NOX1-5 and Duox1-2). We currently have limited knowledge regarding the roles of individual NOX isoforms in diseases, particularly NOX1, which is a major NADPH oxidase isoform in the vasculature but not in leukocytes. In this study, we evaluated the roles of NOX1 in vascular endothelial dysfunction-induced inflammation by recording leukocyte rolling, adherence, and transmigration in a postcapillary venule of rat mesenteric tissue in real time via intravital microscopy. We superfused the mesenteric tissue with Krebs™ buffer, and Krebs™ buffer with a non-selective NO synthase inhibitor, NG-nitro-L-arginine-methyl-ester (L-NAME, 50 µM) with/without a selective NOX1 inhibitor, ML171. We found that at 2 hrs of superfusion, leukocyte rolling (21±8 cells/min), adherence (3±2 cells/100 µm), and transmigration (2±1 cells/200 µm2) was minimal in Krebs™ control (n=8). By contrast, L-NAME (n=6) significantly increased leukocyte rolling (74±12), adhesion (19±6), and transmigration (18±4) (all P<0.05 compared to Krebs™ control). Whereas, ML171 (1 µM, n=7) prevented the L-NAME-induced effect on leukocyte rolling (25±5), adhesion (5±2), and transmigration (5±1). These findings suggest that NOX-1 activation participates in L-NAME induced inflammatory responses; whereas inhibition of NOX1 can mitigate inflammation following vascular endothelial dysfunction.

Publication Title

The FASEB Journal

Volume

30

Issue

1 Supplement

First Page

723.2

Last Page

723.2

Comments

This article was published in The FASEB Journal, Volume 30, Issue 1 Supplement, Pages 723.2-723.2.

The published version is available at http://www.fasebj.org/content/30/1_Supplement/723.2.short .

Copyright © 2016 FASEB.

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