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) Supplemental Figures All Versions of this Article: 296/1/R72    most recent 90718.2008v1 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 Carlström, M. Articles by Persson, A. E. G. Search for Related Content PubMed PubMed Citation Articles by Carlström, M. Articles by Persson, A. E. G.

HEMODYNAMICS AND CARDIORENAL INTEGRATION

Role of NOX2 in the regulation of afferent arteriole responsiveness

¹Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden; ²Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC; ³Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China; ⁴Institute of Vegetative Physiology, University Hospital Charité, Humboldt-University of Berlin, Germany, ⁵Department of Physiology, Monash University, Monash, Australia

Submitted 25 August 2008 ; accepted in final form 29 October 2008

NADPH oxidases (NOX) are the major source of reactive oxygen species (ROS) in the vasculature and contribute to the control of renal perfusion. The role of NOX2 in the regulation of blood pressure and afferent arteriole responsiveness was investigated in NOX2^–/– and wild-type mice. Arteriole constrictions to ANG II (10^–14–10^–6 mol/l) were weaker in NOX2^–/– compared with wild types. N-nitro-L-arginine methyl ester (L-NAME; 10^–4 mol/l) treatment reduced basal diameters significantly more in NOX2^–/– (–18%) than in wild types (–6%) and augmented ANG II responses. Adenosine (10^–11–10^–4 mol/l) constricted arterioles of wild types but not of NOX2^–/–. However, simultaneous inhibition of adenosine type-2 receptors induced vasoconstriction, which was stronger in NOX2^–/–. Adenosine (10^–8 mol/l) enhanced the ANG II response in wild type, but not in NOX2^–/–. This sensitizing effect by adenosine was abolished by apocynin. Chronic ANG II pretreatment (14 days) did not change the ANG II responses in NOX2^–/–, but strengthened the response in wild types. ANG II pretreatment augmented the L-NAME response in NOX2^–/– (–33%), but not in wild types. Simultaneous application of L-NAME and ANG II caused a stronger constriction in the NOX2^–/– (–64%) than in wild types (–46%). Basal blood pressures were similar in both genotypes, however, chronic ANG II infusion elevated blood pressure to a greater extent in wild-type (15 ± 1%) than in NOX2^–/– (8 ± 1%) mice. In conclusion, NOX2 plays an important role in the control of afferent arteriole tone and is involved in the contractile responses to ANG II and/or adenosine. NOX2 can be activated by elevated ANG II and may play an important role in ANG II-induced hypertension. NOX2-derived ROS scavenges nitric oxide, causing subsequent nitric oxide-deficiency.

adenosine; angiotensin II; apocynin; gp91phox; hypertension; L-NAME; nitric oxide; oxidative stress

This article has been cited by other articles:

				S. Matsushima, S. Kinugawa, T. Yokota, N. Inoue, Y. Ohta, S. Hamaguchi, and H. Tsutsui Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H409 - H416. [Abstract] [Full Text] [PDF]

				M. Carlstrom and A. E. G. Persson Important Role of NAD(P)H Oxidase 2 in the Regulation of the Tubuloglomerular Feedback Hypertension, March 1, 2009; 53(3): 456 - 457. [Full Text] [PDF]