Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance L-アルギニン欠乏状態における血管内皮機能異常 : リジン尿性蛋白不耐症患者における検討
Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance
L-アルギニン欠乏状態における血管内皮機能異常 : リジン尿性蛋白不耐症患者における検討
Although L-arginine is the only substrate for nitric oxide (NO) production, no studies have yet been reported on the effect of an L-arginine deficiency on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by mutations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascular endothelial function was examined in an LPI patient who was shown to be a compound heterozygote for two mutations in the gene (5.3-kbp Alu-mediated deletion, IVS3+1G→Α). The lumen diameter of the brachial artery was measured in this patient and in healthy controls at rest, during reactive hyperemia (endothelium-dependent vasodilation [EDV]), and after sublingual nitroglycerin administration (endothelium-independent vasodilation [EIV]) using ultrasonography. Both EDV and NOx concentrations were markedly reduced in the patient compared with those for the controls. They became normal after an L-arginine infusion. EIV was not significantly different between the patient and controls. Positron emission tomography of the heart and a treadmill test revealed ischemic changes in the patient, which were improved by the L-arginine infusion. Thus, in the LPI patient, L-arginine deficiency caused vascular endothelial dysfunction via a decrease in NO production.
Kamada, Yoshihiro; Nagaretani, Hiroyuki; Tamura, Shinji; Ohama, Tohru; Maruyama, Takao; Hiraoka, Hisatoyo; Yamashita, Shizuya; Yamada, Akira; Kiso, Shinichi; Inui, Yoshiaki; Ito, Nobuyuki; Kayanoki, Yoshiro; Kawata, Sumio; Matsuzawa, Yuji. Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient with lysinuric protein intolerance. Journal of Clinical Investigation. 2001. 108(5). p.717-724.