This Article Full Text Full Text (PDF) 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 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 Katusic, Z. S. Search for Related Content PubMed PubMed Citation Articles by Katusic, Z. S.

(Circulation Research. 2007;101:640.)
© 2007 American Heart Association, Inc.

Editorials

Mechanisms of Endothelial Dysfunction Induced by Aging

Role of Arginase I

Zvonimir S. Katusic

From the Departments of Anesthesiology and Pharmacology & Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minn.

Correspondence to Zvonimir S. Katusic, Departments of Anesthesiology and Pharmacology & Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905. E-mail katusic.zvonimir@mayo.edu

See related article, pages 692–702

Key Words: L-arginine • nitric oxide • S-nitrosylation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Impaired production or biological activity of nitric oxide (NO) released from vascular endothelium is a central mechanism of endothelial dysfunction.¹ Large number of published studies demonstrated that endothelial dysfunction is a hallmark of aged endothelium.² Currently, increased concentration of superoxide anion in vascular wall is considered a major mechanism of endothelial dysfunction caused by aging.^3,4,5 Detrimental effect of superoxide anion on aged endothelium is mediated by its chemical reaction with NO leading to inactivation of NO and production of a very potent oxidant, peroxynitrite.⁵ At the present time, there is no consensus in the literature regarding the exact source(s) of superoxide anion in aged blood vessels. Endothelial enzymes known to be potent generators of superoxide anion include NADP(H) oxidase, xanthine oxidase, cyclooxygenases, uncoupled endothelial nitric oxide synthases, as well as respiratory chain enzymes in mitochondria.¹ Besides increase in superoxide anion production, impairment of endothelial nitric oxide synthase (eNOS) enzymatic activity or reduced antioxidant defense capacity of endothelium may also contribute to elevation of superoxide anion concentration and subsequent endothelial dysfunction.^4,5

Optimal intracellular level of amino acid L-arginine, a substrate for eNOS, is a critical factor required for normal biosynthesis of NO. Prior studies by Berkowitz and colleagues⁶ demonstrated that during aging, increased activity of arginase I, (arginase I and arginase II are enzymes that catalyze the hydrolysis of L-arginine to L-ornithine and urea; Figure), may compete for L-arginine with eNOS thereby causing reduced production of NO and endothelial dysfunction. This concept was further supported by the studies demonstrating that . . . [Full Text of this Article]

This article has been cited by other articles:

				E. Jahangir, J. A Vita, D. Handy, M. Holbrook, J. Palmisano, R. Beal, J. Loscalzo, and R. T Eberhardt The effect of l-arginine and creatine on vascular function and homocysteine metabolism Vascular Medicine, August 1, 2009; 14(3): 239 - 248. [Abstract] [PDF]

				P. M. Vanhoutte Arginine and Arginase: Endothelial NO Synthase Double Crossed? Circ. Res., April 25, 2008; 102(8): 866 - 868. [Full Text] [PDF]