Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.
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.
Satterfield
M Carey
MC
Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA.
Bazer
Fuller W
FW
Spencer
Thomas E
TE
Wu
Guoyao
G
D000596:Amino Acids / Q000097:blood*; D000653:Amniotic Fluid / Q000378:metabolism; D000824:Animal Nutritional Physiological Phenomena / Q000187:drug effects; D000818:Animals; D004044:Dietary Proteins / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000517:prevention & control*; D020567:Fetal Weight / Q000187:drug effects*; D005333:Fetus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010920:Placenta / Q000098:blood supply / Q000187:drug effects; D011073:Polyamines / Q000097:blood; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000187:drug effects*; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012756:Sheep; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014471:Umbilical Veins / Q000378:metabolism; D055988:Uterine Artery / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000596:Amino Acids; D004044:Dietary Proteins; D010879:Piperazines; D011073:Polyamines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate