Mendes Ribeiro A C, Brunini T M, Ellory J C, Mann G E
University Laboratory of Physiology, South Parks Road, OX1 3PT, Oxford, UK.
Cardiovasc Res. 2001 Mar;49(4):697-712. doi: 10.1016/s0008-6363(00)00267-4.
Patients with chronic renal and heart failure present with hypertension and widespread vasoconstriction, respectively. Although systemic release of nitric oxide (NO) may be elevated in both pathological syndromes, enhanced production of NO fails to overcome endothelial dysfunction. Plasma concentrations of L-arginine, a cationic amino acid precursor for NO synthesis, are reduced whilst levels of the endogenous L-arginine analogues, asymmetric and symmetric dimethyl arginine and N(G)-monomethyl-L-arginine, seem to be elevated. We have reported that transport of L-arginine via the cationic amino acid transporters y(+)/CAT and/or y(+)L are up-regulated in erythrocytes, peripheral blood mononuclear cells and platelets from both patients with either chronic renal or heart failure. A possible explanation why NO serves as a failing counter-regulatory mechanism in both these pathologies is that availability of L-arginine for NO production is reduced despite the observed increase in membrane transport. This review examines the mechanisms underlying alterations in NO production in chronic renal and heart failure, and the possible role of L-arginine transport in vascular and platelet dysfunction observed in both syndromes.
慢性肾衰竭和心力衰竭患者分别伴有高血压和广泛的血管收缩。尽管在这两种病理综合征中一氧化氮（NO）的全身释放可能都会升高，但NO生成的增加并不能克服内皮功能障碍。作为NO合成的阳离子氨基酸前体，L-精氨酸的血浆浓度降低，而内源性L-精氨酸类似物，即不对称和对称二甲基精氨酸以及N(G)-单甲基-L-精氨酸的水平似乎升高。我们已经报道，无论是慢性肾衰竭患者还是心力衰竭患者，其红细胞、外周血单核细胞和血小板中通过阳离子氨基酸转运体y(+)/CAT和/或y(+)L对L-精氨酸的转运均上调。在这两种疾病中NO作为一种无效的反调节机制的一个可能解释是，尽管观察到膜转运增加，但用于NO生成的L-精氨酸的可用性却降低了。这篇综述探讨了慢性肾衰竭和心力衰竭中NO生成改变的潜在机制，以及L-精氨酸转运在这两种综合征中观察到的血管和血小板功能障碍中的可能作用。
