Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects.

Abstract:

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.

journal_name

Circulation

journal_title

Circulation

authors

Schlaich MP,Parnell MM,Ahlers BA,Finch S,Marshall T,Zhang WZ,Kaye DM

doi

10.1161/01.CIR.0000149748.79945.52

subject

Has Abstract

pub_date

2004-12-14 00:00:00

pages

3680-6

issue

24

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000149748.79945.52

journal_volume

110

pub_type

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