Published Online
on October 10, 2005

A more recent version of this article appeared on October 18, 2005

This Article Full Text (PDF) All Versions of this Article: 112/16/2487    most recent CIRCULATIONAHA.105.543157v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suvorava, T. Articles by Kojda, G. Search for Related Content PubMed PubMed Citation Articles by Suvorava, T. Articles by Kojda, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROGEN PEROXIDE Related Collections Oxidant stress Endothelium/vascular type/nitric oxide Other Vascular biology

Submitted on February 15, 2005
Revised on July 25, 2005
Accepted on July 27, 2005

Endogenous Vascular Hydrogen Peroxide Regulates Arteriolar Tension In Vivo

Tatsiana Suvorava MS, Nadine Lauer PharmD, PhD, Stephanie Kumpf BSc, Ralf Jacob PhD, Wilfried Meyer PhD, and Georg Kojda PharmD, PhD^*

From the Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf (T.S., N.L., S.K., G.K.); the Institut für Zytobiologie und Zytopathologie, Philipps-Universität, Marburg (R.J.); and the Anatomisches Institut, Tierärztliche Hochschule, Hannover (W.M.), Germany.

^* To whom correspondence should be addressed. E-mail: kojda{at}uni-duesseldorf.de.

Background--Although many studies suggested direct vasomotor effects of hydrogen peroxide (H₂O₂) in vitro, little is known about the vasomotor effects of H₂O₂ in vivo.

Methods and Results--We have generated mice overexpressing human catalase driven by the Tie-2 promoter to specifically target this transgene to the vascular tissue. Vessels of these mice (cat⁺⁺) expressed significantly higher levels of catalase mRNA, protein, and activity. The overexpression was selective for vascular tissue, as evidenced by immunohistochemistry in specimens of aorta, heart, lung, and kidney. Quantification of reactive oxygen species by fluorescence signals in cat⁺⁺ versus catalase-negative (catⁿ) mice showed a strong decrease in aortic endothelium and left ventricular myocardium but not in leukocytes. Awake male cat⁺⁺ at 3 to 4 months of age had a significantly lower systolic blood pressure (sBP, 102.7±2.2 mm Hg, n=10) compared with their transgene-negative littermates (catⁿ, 115.6±2.5 mm Hg, P=0.0211) and C57BL/6 mice (118.4±3.06 mm Hg, n=6). Treatment with the catalase inhibitor aminotriazole increased sBP of cat⁺⁺ to 117.3±4.3 mm Hg (P=0.0345), while having no effect in catⁿ (118.4±2.4 mm Hg, n=4, P>0.05). In contrast, treatment with the NO-synthase inhibitor nitro-L-arginine methyl ester (100 mg · kg BW^-1 · d^-1) increased sBP in cat⁺⁺ and C57Bl/6 to a similar extent. Likewise, phosphorylation of vasodilator-stimulated phosphoprotein in skeletal muscle, left ventricular myocardium, and lung was identical in cat⁺⁺ and catⁿ. Endothelium- and NO-dependent aortic vasodilations were unchanged in cat⁺⁺. Aortic KCl contractions were significantly lower in cat⁺⁺ and exogenous H₂O₂ (10 µmol/L)-induced vasoconstriction.

Conclusions--These data suggest that endogenous H₂O₂ may act as a vasoconstrictor in resistance vessels and contribute to the regulation of blood pressure.

Key words: hydrogen peroxide • blood pressure • catalase, vascular • aminotriazole • contractility

This article has been cited by other articles:

				J. Belik, M. Jerkic, B. A. S. McIntyre, J. Pan, J. Leen, L. X. Yu, R. M. Henkelman, M. Toporsian, and M. Letarte Age-dependent endothelial nitric oxide synthase uncoupling in pulmonary arteries of endoglin heterozygous mice Am J Physiol Lung Cell Mol Physiol, December 1, 2009; 297(6): L1170 - L1178. [Abstract] [Full Text] [PDF]

				L. Gao and G. E. Mann Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling Cardiovasc Res, April 1, 2009; 82(1): 9 - 20. [Abstract] [Full Text] [PDF]

				P. Sun, W. Liu, D.-H. Lin, P. Yue, R. Kemp, L. M. Satlin, and W.-H. Wang Epoxyeicosatrienoic Acid Activates BK Channels in the Cortical Collecting Duct J. Am. Soc. Nephrol., March 1, 2009; 20(3): 513 - 523. [Abstract] [Full Text] [PDF]

				L. S. A. Capettini, S. F. Cortes, M. A. Gomes, G. A. B. Silva, J. L. Pesquero, M. J. Lopes, M. M. Teixeira, and V. S. Lemos Neuronal nitric oxide synthase-derived hydrogen peroxide is a major endothelium-dependent relaxing factor Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2503 - H2511. [Abstract] [Full Text] [PDF]

				P. A. Rogers, G. M. Dick, J. D. Knudson, M. Focardi, I. N. Bratz, A. N. Swafford Jr., S.-i. Saitoh, J. D. Tune, and W. M. Chilian H2O2-induced redox-sensitive coronary vasodilation is mediated by 4-aminopyridine-sensitive K+ channels Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2473 - H2482. [Abstract] [Full Text] [PDF]

				F. M. Faraci Hydrogen peroxide: watery fuel for change in vascular biology. Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1931 - 1933. [Full Text] [PDF]

				R. M. Touyz Mitochondrial Redox Control of Matrix Metalloproteinase Signaling in Resistance Arteries Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 685 - 688. [Full Text] [PDF]

				N. Ardanaz and P. J. Pagano Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Experimental Biology and Medicine, March 1, 2006; 231(3): 237 - 251. [Abstract] [Full Text] [PDF]