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

Article

关键词: ORAL L-ARGININE;    DEPENDENT VASCULAR RELAXATION;    CORONARY-ARTERY-DISEASE;    NITRIC-OXIDE SYNTHASE;    HUMAN HEART-FAILURE;    HUMANS;    PLASMA;    PLETHYSMOGRAPHY;    PARADOX;    CELLS;   

DOI  :  10.1161/01.CIR.0000149748.79945.52

来源: SCIE

【 摘 要 】

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 ([H-3] 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.

【 授权许可】

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