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(Circulation. 2004;110:3680-3686.)
© 2004 American Heart Association, Inc.

Hypertension

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; David M. Kaye, MD, PhD

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

Correspondence to Dr David Kaye, Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, PO Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia. E-mail david.kaye{at}baker.edu.au

Received July 5, 2004; accepted August 9, 2004.

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

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