Schlaich Markus P, Parnell Melinda M, Ahlers Belinda A, Finch Samara, Marshall Tanneale, Zhang Wei-Zheng, Kaye David M
Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Circulation. 2004 Dec 14;110(24):3680-6. doi: 10.1161/01.CIR.0000149748.79945.52. Epub 2004 Nov 29.
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.
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.
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.
内皮依赖性一氧化氮介导的血管舒张功能受损是原发性高血压的关键特征，且可能先于血压升高出现。我们研究了一氧化氮前体L-精氨酸的转运是否与内皮功能降低有关。
使用放射性示踪动力学（[3H]L-精氨酸）来测量高血压患者（n = 12）以及有（n = 15）和无（n = 15）高血压家族史的两组健康志愿者的前臂和外周血单核细胞精氨酸摄取。同时，在动脉内补充输注L-精氨酸前后，测量前臂血流对乙酰胆碱和硝普钠的反应。与无高血压家族史组相比，原发性高血压组和有高血压家族史组的L-精氨酸转运的体内和体外测量值均显著降低；然而，阳离子氨基酸转运体CAT-1在外周血单核细胞的mRNA或蛋白表达水平上未检测到差异。各组间L-精氨酸和N(G),N(G')-二甲基精氨酸（ADMA）的血浆浓度无差异。仅在原发性高血压且有高血压家族史的受试者中，补充L-精氨酸改善了对乙酰胆碱的反应。
与高血压患者相似，有高血压发病高风险的血压正常个体的特征是L-精氨酸转运受损，这可能代表了有缺陷的L-精氨酸/一氧化氮途径与原发性高血压发病之间的联系。观察到的转运缺陷并非由于CAT-1表达的明显改变或内源性ADMA升高所致。
