Next Article in Journal
Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway
Previous Article in Journal
A Systematic Review of the Efficacy of Bioactive Compounds in Cardiovascular Disease: Phenolic Compounds
Article Menu

Export Article

Open AccessArticle
Nutrients 2015, 7(7), 5217-5238;

Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands
Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6200, The Netherlands
Department of Molecular Biomedical Research, VIB, Ghent B-9000, Belgium
Department of Biomedical Molecular Biology, Ghent University, Ghent B-9000, Belgium
Department of Anatomy & Embryology, Maastricht University Medical Center, Maastricht 6200, The Netherlands
Author to whom correspondence should be addressed.
Received: 12 May 2015 / Revised: 15 May 2015 / Accepted: 18 June 2015 / Published: 29 June 2015
Full-Text   |   PDF [1768 KB, uploaded 29 June 2015]   |  


Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues. View Full-Text
Keywords: arginase; arginine; citrulline; microcirculation; nitric oxide arginase; arginine; citrulline; microcirculation; nitric oxide

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Wijnands, K.A.; Meesters, D.M.; van Barneveld, K.W.; Visschers, R.G.; Briedé, J.J.; Vandendriessche, B.; van Eijk, H.M.; Bessems, B.A.; Hoven, N.; von Wintersdorff, C.J.; Brouckaert, P.; Bouvy, N.D.; Lamers, W.H.; Cauwels, A.; Poeze, M. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity. Nutrients 2015, 7, 5217-5238.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top