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: 295/3/H1008    most recent 00114.2008v1 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 Zhou, X. Articles by Unthank, J. L. Search for Related Content PubMed PubMed Citation Articles by Zhou, X. Articles by Unthank, J. L.

NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo

Departments of ¹Surgery and ²Cellular and Integrative Physiology, Indiana University Medical Center, Indianapolis, Indiana

Submitted 4 February 2008 ; accepted in final form 1 July 2008

Nitric oxide (NO) and reactive oxygen species (ROS) have fundamentally important roles in the regulation of vascular tone and remodeling. Although arterial disease and endothelial dysfunction alter NO and ROS levels to impact vasodilation and vascular structure, direct measurements of these reactive species under in vivo conditions with flow alterations are unavailable. In this study, in vivo measurements of NO and H₂O₂ were made on mesenteric arteries to determine whether antioxidant therapies could restore normal NO production in spontaneously hypertensive rats (SHR). Flow was altered from 50–200% of control in anesthetized Wistar-Kyoto rats (WKY) and SHR by selective placement of microvascular clamps on adjacent arteries while NO and H₂O₂ were directly measured with microelectrodes. Relative to WKY, SHR had significantly increased baseline NO and H₂O₂ concentrations (2,572 ± 241 vs. 1,059 ± 160 nM, P < 0.01; and 26 ± 7 vs. 7 ± 1 µM, P < 0.05, respectively). With flow elevation, H₂O₂ but not NO increased in SHR; NO but not H₂O₂ was elevated in WKY. Apocynin and polyethylene-glycolated catalase decreased baseline SHR NO and H₂O₂ to WKY levels and restored flow-mediated NO production. Suppression of NAD(P)H oxidase with gp91ds-tat decreased SHR H₂O₂ to WKY levels. Addition of topical H₂O₂ to increase peroxide to the basal concentration measured in SHR elevated WKY NO to levels observed in SHR. The results support the hypothesis that increased vascular peroxide in SHR is primarily derived from NAD(P)H oxidase and increases NO concentration to levels that cannot be further elevated with increased flow. Short-term and even acute administration of antioxidants are able to restore normal flow-mediated NO signaling in young SHR.

hypertension; oxidative stress; flow mediated; NAD(P)H oxidase inhibition; spontaneously hypertensive rats

This article has been cited by other articles:

				X. Zhou, H. G. Bohlen, J. L. Unthank, and S. J. Miller Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2227 - H2233. [Abstract] [Full Text] [PDF]

				H. G. Bohlen, X. Zhou, J. L. Unthank, S. J. Miller, and R. Bills Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1337 - H1346. [Abstract] [Full Text] [PDF]

				M. A. Potenza, S. Gagliardi, L. De Benedictis, A. Zigrino, E. Tiravanti, G. Colantuono, A. Federici, L. Lorusso, V. Benagiano, M. J. Quon, et al. Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E685 - E694. [Abstract] [Full Text] [PDF]

				A. S. Godbole, X. Lu, X. Guo, and G. S. Kassab NADPH oxidase has a directional response to shear stress Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H152 - H158. [Abstract] [Full Text] [PDF]