Department of Animal Science, Texas A&M University, College Station, TX 77843-2471, USA.
J Nutr. 2010 Feb;140(2):251-8. doi: 10.3945/jn.109.114678. Epub 2009 Dec 16.
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.
充足的胎盘血流对于从母体向胎儿输送营养物质以促进胚胎生长至关重要。胎儿发育受限是由改变子宫胎盘血流、胎盘功能的病理生理和环境因素引起的，因此也会改变胎儿的营养供应。为了验证这一假说，从妊娠第 28 天至 115 天，每天给接受限制营养（NRC 需求的 50%）或充分营养（NRC 需求的 100%）的母羊皮下注射 0、75 或 150mg/d 的西地那非（伟哥）。在第 115 天，收集母羊、胎儿和胎盘组织和液体。与充分营养的母羊相比，限制营养的母羊子宫静脉和动脉血清、羊水和尿囊液以及胎儿脐静脉血清中的总氨基酸和多胺浓度更低（P<0.05），胎儿脐静脉血清中总氨基酸与子宫动脉血清的比值也更低。西地那非剂量依赖性地增加（P<0.05）了羊水、尿囊液和胎儿血清中的总氨基酸和多胺，而对母血清中的值没有影响。第 115 天，限制营养的母羊的胎儿体重更低（P<0.05）。西地那非治疗剂量依赖性地增加了限制营养和充分营养的母羊的胎儿体重（P<0.05）。本研究支持长期西地那非治疗通过增加胚胎中氨基酸的可用性来增强胎儿生长的假说，至少部分如此。这些发现可能导致在怀疑有宫内胎儿生长迟缓风险的人类妊娠中临床应用西地那非。
