QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online Supplemental Material All Versions of this Article: 139/4/660    most recent jn.108.102020v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lassala, A. Articles by Wu, G. Search for Related Content PubMed PubMed Citation Articles by Lassala, A. Articles by Wu, G.

---

Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Intravenous Administration of L-Citrulline to Pregnant Ewes Is More Effective Than L-Arginine for Increasing Arginine Availability in the Fetus^1–3,

⁴ Department of Animal Science and ⁵ Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843

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.

^* To whom correspondence should be addressed. E-mail: g-wu{at}tamu.edu.

Manuscript received 5 November 2008. Initial review completed 14 January 2009. Revision accepted 23 January 2009.

Published online 18 February 2009.