Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity
AbstractEnhanced 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
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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.
Wijnands KA, Meesters DM, van Barneveld KW, Visschers RG, Briedé JJ, Vandendriessche B, van Eijk HM, Bessems BA, Hoven N, von Wintersdorff CJ, Brouckaert P, Bouvy ND, Lamers WH, Cauwels A, Poeze M. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity. Nutrients. 2015; 7(7):5217-5238.Chicago/Turabian Style
Wijnands, Karolina A.; Meesters, Dennis M.; van Barneveld, Kevin W.; Visschers, Ruben G.; Briedé, Jacob J.; Vandendriessche, Benjamin; van Eijk, Hans M.; Bessems, Babs A.; Hoven, Nadine ; von Wintersdorff, Christian J.; Brouckaert, Peter; Bouvy, Nicole D.; Lamers, Wouter H.; Cauwels, Anje; Poeze, Martijn. 2015. "Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity." Nutrients 7, no. 7: 5217-5238.