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Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity

(2015) NUTRIENTS. 7(7). p.5217-5238
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Abstract
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.
Keywords
citrulline, microcirculation, arginine, arginase, NITRIC-OXIDE PRODUCTION, SICKLE-CELL-DISEASE, nitric oxide, AMINO-ACID TRANSPORTERS, PULMONARY-HYPERTENSION, OXIDATIVE STRESS, THERAPY, SEPSIS, MICROCIRCULATION, MICE, DEFICIENCY

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MLA
Wijnands, Karolina AP et al. “Citrulline Supplementation Improves Organ Perfusion and Arginine Availability Under Conditions with Enhanced Arginase Activity.” NUTRIENTS 7.7 (2015): 5217–5238. Print.
APA
Wijnands, K. A., Meesters, D. M., van Barneveld, K. W., Visschers, R. G., Briedé, J. J., Vandendriessche, B., van Eijk, H. M., et al. (2015). Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity. NUTRIENTS, 7(7), 5217–5238.
Chicago author-date
Wijnands, Karolina AP, Dennis M Meesters, Kevin WY van Barneveld, Ruben GJ Visschers, Jacob J Briedé, Benjamin Vandendriessche, Hans MH van Eijk, et al. 2015. “Citrulline Supplementation Improves Organ Perfusion and Arginine Availability Under Conditions with Enhanced Arginase Activity.” Nutrients 7 (7): 5217–5238.
Chicago author-date (all authors)
Wijnands, Karolina AP, Dennis M Meesters, Kevin WY van Barneveld, Ruben GJ Visschers, Jacob J Briedé, Benjamin Vandendriessche, Hans MH van Eijk, Babs AFM Bessems, Nadine van den Hoven, Christian JH von Wintersdorff, Peter Brouckaert, Nicole D Bouvy, Wouter H Lamers, Anje Cauwels, and Martijn Poeze. 2015. “Citrulline Supplementation Improves Organ Perfusion and Arginine Availability Under Conditions with Enhanced Arginase Activity.” Nutrients 7 (7): 5217–5238.
Vancouver
1.
Wijnands KA, Meesters DM, van Barneveld KW, Visschers RG, Briedé JJ, Vandendriessche B, et al. Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity. NUTRIENTS. 2015;7(7):5217–38.
IEEE
[1]
K. A. Wijnands et al., “Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity,” NUTRIENTS, vol. 7, no. 7, pp. 5217–5238, 2015.
@article{6971821,
  abstract     = {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.},
  author       = {Wijnands, Karolina AP and Meesters, Dennis M and van Barneveld, Kevin WY and Visschers, Ruben GJ and Briedé, Jacob J and Vandendriessche, Benjamin and van Eijk, Hans MH and Bessems, Babs AFM and van den Hoven, Nadine and von Wintersdorff, Christian JH and Brouckaert, Peter and Bouvy, Nicole D and Lamers, Wouter H and Cauwels, Anje and Poeze, Martijn},
  issn         = {2072-6643},
  journal      = {NUTRIENTS},
  keywords     = {citrulline,microcirculation,arginine,arginase,NITRIC-OXIDE PRODUCTION,SICKLE-CELL-DISEASE,nitric oxide,AMINO-ACID TRANSPORTERS,PULMONARY-HYPERTENSION,OXIDATIVE STRESS,THERAPY,SEPSIS,MICROCIRCULATION,MICE,DEFICIENCY},
  language     = {eng},
  number       = {7},
  pages        = {5217--5238},
  title        = {Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity},
  url          = {http://dx.doi.org/10.3390/nu7075217},
  volume       = {7},
  year         = {2015},
}

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