Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles

Vascular endothelial function deteriorates with age and disease, and the production of vasodilator factors like nitric oxide (NO) decreases. The free amino acid l-citrulline increases vasodilation and blood flow through increased NO production. We examined the effects of oral l-citrulline administra...

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Main Authors: Sho Miyatake, Kazuo Hino, Goro Ebisu, Satoshi Fujita
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580821002430
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author Sho Miyatake
Kazuo Hino
Goro Ebisu
Satoshi Fujita
author_facet Sho Miyatake
Kazuo Hino
Goro Ebisu
Satoshi Fujita
author_sort Sho Miyatake
collection DOAJ
description Vascular endothelial function deteriorates with age and disease, and the production of vasodilator factors like nitric oxide (NO) decreases. The free amino acid l-citrulline increases vasodilation and blood flow through increased NO production. We examined the effects of oral l-citrulline administration on vascular delivery of substances to skeletal muscles. In Experiment 1, following oral l-citrulline administration and subsequent intravenous Evans blue dye (EBD) administration to rats, EBD levels delivered to skeletal muscles were measured after 60 min. In Experiment 2, plasma concentrations of amino acids and NOx, an indicator of vasodilation, were measured over time after oral l-citrulline administration. In Experiment 3, we measured EBD levels in skeletal muscles of streptozotocin-induced type 1 diabetic rats following l-citrulline administration. In these experiments, EBD levels in the soleus muscle were higher in the l-citrulline group than in the control group (19.9 ± 0.7 vs. 22.5 ± 1.9 μg/g tissue, p < 0.05). Plasma l-arginine, l-citrulline, and NOx levels were increased within 30 min after l-citrulline administration. EBD levels in the soleus and gastrocnemius muscles were higher in diabetic rats with l-citrulline administration (18.7 ± 2.2 vs. 25.0 ± 4.3 μg/g tissue, p < 0.05 and 8.0 ± 0.5 vs. 9.2 ± 0.8 μg/g tissue, p = 0.05, respectively). These data suggest that oral l-citrulline administration may increase the level of substances delivered to skeletal muscles by increasing the NO production in both normal and vascular endothelial dysfunction models.
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spelling doaj.art-29a979d539bc4ccca1e7253ccbfb8d7a2022-12-21T18:43:35ZengElsevierBiochemistry and Biophysics Reports2405-58082021-12-0128101149Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal musclesSho Miyatake0Kazuo Hino1Goro Ebisu2Satoshi Fujita3OS-1 Division, Medical Foods Research Institute, Otsuka Pharmaceutical Factory, Inc., 115 Kuguhara, Tateiwa, Muya-cho, Naruto, Tokushima, 772-8601, Japan; Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1, Nojihigashi, Kusatsu, Shiga, 525-8577, JapanOS-1 Division, Medical Foods Research Institute, Otsuka Pharmaceutical Factory, Inc., 115 Kuguhara, Tateiwa, Muya-cho, Naruto, Tokushima, 772-8601, JapanOS-1 Division, Medical Foods Research Institute, Otsuka Pharmaceutical Factory, Inc., 115 Kuguhara, Tateiwa, Muya-cho, Naruto, Tokushima, 772-8601, JapanFaculty of Sport and Health Science, Ritsumeikan University, 1-1-1, Nojihigashi, Kusatsu, Shiga, 525-8577, Japan; Corresponding author.Vascular endothelial function deteriorates with age and disease, and the production of vasodilator factors like nitric oxide (NO) decreases. The free amino acid l-citrulline increases vasodilation and blood flow through increased NO production. We examined the effects of oral l-citrulline administration on vascular delivery of substances to skeletal muscles. In Experiment 1, following oral l-citrulline administration and subsequent intravenous Evans blue dye (EBD) administration to rats, EBD levels delivered to skeletal muscles were measured after 60 min. In Experiment 2, plasma concentrations of amino acids and NOx, an indicator of vasodilation, were measured over time after oral l-citrulline administration. In Experiment 3, we measured EBD levels in skeletal muscles of streptozotocin-induced type 1 diabetic rats following l-citrulline administration. In these experiments, EBD levels in the soleus muscle were higher in the l-citrulline group than in the control group (19.9 ± 0.7 vs. 22.5 ± 1.9 μg/g tissue, p < 0.05). Plasma l-arginine, l-citrulline, and NOx levels were increased within 30 min after l-citrulline administration. EBD levels in the soleus and gastrocnemius muscles were higher in diabetic rats with l-citrulline administration (18.7 ± 2.2 vs. 25.0 ± 4.3 μg/g tissue, p < 0.05 and 8.0 ± 0.5 vs. 9.2 ± 0.8 μg/g tissue, p = 0.05, respectively). These data suggest that oral l-citrulline administration may increase the level of substances delivered to skeletal muscles by increasing the NO production in both normal and vascular endothelial dysfunction models.http://www.sciencedirect.com/science/article/pii/S2405580821002430l-citrullineSkeletal muscleVascular endotheliumDiabetesNitric oxide
spellingShingle Sho Miyatake
Kazuo Hino
Goro Ebisu
Satoshi Fujita
Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles
Biochemistry and Biophysics Reports
l-citrulline
Skeletal muscle
Vascular endothelium
Diabetes
Nitric oxide
title Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles
title_full Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles
title_fullStr Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles
title_full_unstemmed Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles
title_short Oral administration of l-citrulline alters the vascular delivery of substances to rat skeletal muscles
title_sort oral administration of l citrulline alters the vascular delivery of substances to rat skeletal muscles
topic l-citrulline
Skeletal muscle
Vascular endothelium
Diabetes
Nitric oxide
url http://www.sciencedirect.com/science/article/pii/S2405580821002430
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AT goroebisu oraladministrationoflcitrullinealtersthevasculardeliveryofsubstancestoratskeletalmuscles
AT satoshifujita oraladministrationoflcitrullinealtersthevasculardeliveryofsubstancestoratskeletalmuscles