Published Online
on November 29, 2004

A more recent version of this article appeared on December 14, 2004

This Article Full Text (PDF) All Versions of this Article: 110/24/3680    most recent 01.CIR.0000149748.79945.52v1 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 Schlaich, M. P. Articles by Kaye, D. M. Search for Related Content PubMed PubMed Citation Articles by Schlaich, M. P. Articles by Kaye, D. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE NITRIC OXIDE Medline Plus Health Information High Blood Pressure Related Collections Hypertension - basic studies Clinical Studies Endothelium/vascular type/nitric oxide Related Article

Submitted on July 5, 2004
Accepted on August 9, 2004

Impaired L-Arginine Transport and Endothelial Function in Hypertensive and Genetically Predisposed Normotensive Subjects

Markus P. Schlaich MD, Melinda M. Parnell PhD, Belinda A. Ahlers PhD, Samara Finch BSc, Tanneale Marshall BSc, Wei-Zheng Zhang PhD, and David M. Kaye MD, PhD^*

From the Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, Melbourne, Victoria, Australia.

^* To whom correspondence should be addressed. E-mail: david.kaye{at}baker.edu.au.

Background--Impaired endothelium-dependent NO-mediated vasodilation is a key feature of essential hypertension and may precede the increase in blood pressure. We investigated whether transport of the NO precursor L-arginine is related to decreased endothelial function.

Methods and Results--Radiotracer kinetics ([³H]L-arginine) were used to measure forearm and peripheral blood mononuclear cell arginine uptake in hypertensive subjects (n=12) and in 2 groups of healthy volunteers with (n=15) and without (n=15) a family history of hypertension. In conjunction, forearm blood flow responses to acetylcholine and sodium nitroprusside were measured before and after a supplemental intra-arterial infusion of L-arginine. In vivo and in vitro measures of L-arginine transport were substantially reduced in the essential hypertension and positive family history groups compared with the negative family history group; however, no difference was detected in peripheral blood mononuclear cell mRNA or protein expression levels for the cationic amino acid transporter CAT-1. Plasma concentrations of L-arginine and N^G,N^G`-dimethylarginine (ADMA) did not differ between groups. L-Arginine supplementation improved the response to acetylcholine only in subjects with essential hypertension and positive family history.

Conclusions--Similar to their hypertensive counterparts, normotensive individuals at high risk for the development of hypertension are characterized by impaired L-arginine transport, which may represent the link between a defective L-arginine/NO pathway and the onset of essential hypertension. The observed transport defect is not due to apparent alterations in CAT-1 expression or elevated endogenous ADMA.

Key words: hypertension • endothelium • nitric oxide • amino acids • arginine

Related Article:

Issue Highlights
Circulation 2004 110: 3617. [Extract] [Full Text]

This article has been cited by other articles:

				W.H. W. Tang, Z. Wang, L. Cho, D. M. Brennan, and S. L. Hazen Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2061 - 2067. [Abstract] [Full Text] [PDF]

				D. Wang, S. Strandgaard, J. Iversen, and C. S. Wilcox Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R195 - R200. [Abstract] [Full Text] [PDF]

				E. Gkaliagkousi, J. Ritter, and A. Ferro Platelet-Derived Nitric Oxide Signaling and Regulation Circ. Res., September 28, 2007; 101(7): 654 - 662. [Abstract] [Full Text] [PDF]

				L. A. Holowatz and W. L. Kenney Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans J. Physiol., June 1, 2007; 581(2): 863 - 872. [Abstract] [Full Text] [PDF]

				Z. Yang, K. Venardos, E. Jones, B. J. Morris, J. Chin-Dusting, and D. M. Kaye Identification of a Novel Polymorphism in the 3'UTR of the L-Arginine Transporter Gene SLC7A1: Contribution to Hypertension and Endothelial Dysfunction Circulation, March 13, 2007; 115(10): 1269 - 1274. [Abstract] [Full Text] [PDF]

				M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]

				R. A. Augustyniak, R. G. Victor, D. A. Morgan, and W. Zhang L-NAME- and ADMA-induced sympathetic neural activation in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R726 - R732. [Abstract] [Full Text] [PDF]