Intravenous Administration of L-Citrulline to Pregnant Ewes Is More Effective Than L-Arginine for Increasing Arginine Availability in the Fetus
Open Access
- 1 April 2009
- journal article
- Published by Elsevier BV in Journal of Nutrition
- Vol. 139 (4), 660-665
- https://doi.org/10.3945/jn.108.102020
Abstract
L-Arginine administration may be useful for the treatment of intrauterine growth restriction, but concerns remain about effective precursors for administration into pregnant dams. Therefore, we used an ovine model to test the hypothesis that infusion of L-citrulline into the maternal circulation increases L-arginine availability to the fetus. On d 135 ± 1 of gestation, ewes received an i.v. bolus dose of L-citrulline (155 μmol/kg body weight) or the same dose of L-arginine-HCl. Maternal and fetal arterial blood samples were obtained simultaneously at −120, −60, 0, 5, 15, 30, 60, 120, 180, and 240 min relative to the time of amino acid administration. Concentrations of arginine in maternal plasma increased to peak values within 5 min after its injection in ewes and declined rapidly thereafter, whereas concentrations of arginine in fetal plasma increased between 15 and 30 min and returned to baseline values by 60 min. In contrast, administration of citrulline increased concentrations of citrulline and arginine in maternal and fetal plasma between 5 and 60 min and values remained elevated thereafter. The differential pharmacokinetics for arginine compared with citrulline infusion was consistent with the observation that the half-life of citrulline was twice that of arginine in ewes. We conclude that i.v. administration of citrulline is more effective than arginine in sustaining high concentrations of arginine in the maternal and fetal circulations of pregnant ewes. These novel findings provide support for studies of the clinical use of arginine and citrulline as therapeutic means to prevent or ameliorate fetal growth retardation in mammals.Keywords
This publication has 44 references indexed in Scilit:
- Arginine metabolism and nutrition in growth, health and diseaseAmino Acids, 2008
- Proline metabolism in the conceptus: implications for fetal growth and developmentAmino Acids, 2008
- Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic studyBritish Journal of Nutrition, 2007
- Potential Effects of Nutrients on Placental Function and Fetal GrowthPublished by S. Karger AG ,2005
- l‐Arginine treatment for asymmetric fetal growth restrictionInternational Journal of Gynecology & Obstetrics, 2004
- Maternal Nutrient Restriction Reduces Concentrations of Amino Acids and Polyamines in Ovine Maternal and Fetal Plasma and Fetal Fluids1Biology of Reproduction, 2004
- Developmental Changes of Amino Acids in Ovine Fetal Fluids1Biology of Reproduction, 2003
- Inhibition of placental ornithine decarboxylase by DL-α-difluoro-methyl ornithine causes fetal growth restriction in ratLife Sciences, 2002
- Impact of the L-Arginine/Nitric Oxide System in PregnancyObstetrical & Gynecological Survey, 1995
- Placental nitric oxide metabolismReproduction, Fertility and Development, 1995