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J. Nutr. First published December 16, 2009; doi:10.3945/jn.109.114678
 Journal of Nutrition, doi:10.3945/jn.109.114678
Vol. 140, No. 2, 251-258, February 2010
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© 2010 American Society for Nutrition

Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Sildenafil Citrate Treatment Enhances Amino Acid Availability in the Conceptus and Fetal Growth in an Ovine Model of Intrauterine Growth Restriction1–3,

M. Carey Satterfield, Fuller W. Bazer, Thomas E. Spencer and Guoyao Wu*

Department of Animal Science, Texas A&M University, College Station, TX 77843-2471

Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

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

Manuscript received 18 August 2009. Initial review completed 22 September 2009. Revision accepted 11 November 2009.

Published online 16 December 2009.




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A. Lassala, F. W. Bazer, T. A. Cudd, S. Datta, D. H. Keisler, M. C. Satterfield, T. E. Spencer, and G. Wu
Parenteral Administration of L-Arginine Prevents Fetal Growth Restriction in Undernourished Ewes
J. Nutr., July 1, 2010; 140(7): 1242 - 1248.
[Abstract] [Full Text] [PDF]