Vascular endothelial dysfunction resulting from L-arginine deficiency in a patient 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 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-->A). 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 NO(x) 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
Y
Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Nagaretani
H
H
Tamura
S
S
Ohama
T
T
Maruyama
T
T
Hiraoka
H
H
Yamashita
S
S
Yamada
A
A
Kiso
S
S
Inui
Y
Y
Ito
N
N
Kayanoki
Y
Y
Kawata
S
S
Matsuzawa
Y
Y
D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D017023:Coronary Angiography; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005080:Exercise Test; D006321:Heart / Q000000981:diagnostic imaging; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009569:Nitric Oxide / Q000097:blood; D014055:Tomography, Emission-Computed; D014664:Vasodilation / Q000187:drug effects
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins; D009569:Nitric Oxide; D001120:Arginine