Vascular endothelial dysfunction resulting from L-arginine deficiency in apatient with lysinuric protein intolerance

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 deficienc y on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by m utations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascula r 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 -->A). The lumen diameter of the brachial artery was meas ured in this patient and in healthy controls at rest, during reactive hyper emia (endothelium-dependent vasodilation [EDV]), and after sublingual nitro glycerin administration (endothelium-independent vasodilation [EIV]) using ultrasonography. Both EDV and NO, concentrations were markedly reduced in t he patient compared with those for the controls. They became normal after a n L-arginine infusion. EIV was not significantly different between the pati ent 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.