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Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability
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BACKGROUND: Chronic supplementation with L-citrulline plus L-arginine has been shown to exhibit anti-atherosclerotic effects. However, the short-term action of this combination on the nitric oxide (NO)-cGMP pathway remains to be elucidated. The objective of the present study was to investigate the acute effects of a combination of oral L-citrulline and L-arginine on plasma L-arginine and NO levels, as well as on blood circulation. METHODS: Rats or New Zealand white rabbits were treated orally with L-citrulline, or L-arginine, or a combination of each at half dosage. Following supplementation, plasma levels of L-arginine, NOx, cGMP and changes in blood circulation were determined sequentially. RESULTS: L-Citrulline plus L-arginine supplementation caused a more rapid increase in plasma L-arginine levels and marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids. Blood flow in the central ear artery in rabbits was also significantly increased by L-citrulline plus L-arginine administration as compared with the control. CONCLUSION: Our data show for the first time that a combination of oral L-citrulline and L-arginine effectively and rapidly augments NO-dependent responses at the acute stage. This approach may have clinical utility for the regulation of cardiovascular function in humans.
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“Citrulline, the end product of arginine-mediated nitric oxide production, has shown the potential to increase plasma nitrate and NO availability (Schwedhelm et al. 2007; Morita et al. 2014).”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Morita et al. 2014
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“enhanced the bioavailability of nitric oxide (Morita et al. 2014)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Morita et al. 2014
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Metadata
- Authors
- Morita, M., Hayashi, T., Ochiai, M., Maeda, M., Yamaguchi, T., Ina, K., & Kuzuya, M.
- Affiliations
- Nagoya University (JP)
- Corresponding author
- Hayashi, Toshio
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 454
- Issue
- 1
- Pages
- 53-57
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2058486417
- Cited by
- 140
- References
- 36
- Citations by year
- 2026: 14 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 17 · 2019: 17 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 2
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- KYOWA HAKKO BIO CO., LTD
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology (medical) › Biochemical effects in animals
- Keywords
- citrulline, L-arginine, amino acid supplementation, nitric oxide bioavailability, nitric oxide-cGMP pathway, cyclic GMP, blood flow, ear artery, cardiovascular function, atherosclerosis
- MeSH terms
- Administration, Oral, Animals, Arginine, Biological Availability, Citrulline, Drug Synergism, Cyclic GMP, Humans, Male, Nitric Oxide, Rabbits, Signal Transduction, Rats, Sprague-Dawley, Dietary Supplements, Atherosclerosis, Rats
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