Arginine and fetal growth in ovine models of intrauterine growth restriction



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This research was conducted to test the hypothesis that parenteralarginine supplementation is effective in enhancing birth weights of intrauterinegrowth restricted (IUGR) fetuses. Underfed and prolific ewes were used asexperimental models. The first study characterized the pharmacokinetics ofarginine and citrulline and assessed the potential of citrulline to serve as aprecursor for enhancing arginine availability in fetal and maternal plasma. Sixlate pregnant ewes and their fetuses were instrumented to access arterial andvenous circulations. Intravenous boluses of 155 mol of L-arginine-HCl or Lcitrullineper kg body weight were administered to each ewe. Administration ofcitrulline was more effective than arginine in achieving a sustained increase inconcentrations of arginine in maternal and fetal blood. Accordingly, theclearance rate of citrulline was lower and its biological half-life in maternal bloodgreater, when compared with arginine. The second experiment determined ifadministration of arginine to underfed ewes is effective in ameliorating orpreventing IUGR. Ewes were fed either 100% or 50% of the National ResearchCouncil recommended nutrient requirements for pregnant sheep. Between Day60 of pregnancy and parturition control-fed ewes received saline solution and underfed ewes received either saline solution or L-arginine-HCl solution (155mol of arginine/kg body weight) intravenously three times daily (n=5 / treatmentgroup). Birth weights of lambs were lower in saline-infused underfed ewes.There was no difference in birth weights of lambs from control-fed and argininetreatedunderfed ewes. The third experiment determined whether administrationof arginine could improve survival rates of lambs and enhance fetal growth inewes carrying multiple fetuses. Between Days 100 and 121 of pregnancy, ewesreceived an intravenous infusion of either saline solution (n= 14) or L-arginine-HCl solution (345 mol of arginine/kg body weight, n=20) three times daily.Parenteral administration of arginine increased the percentage of lambs bornalive and enhanced the birth weights of quadruplets. Collectively, these resultsindicate that 1) parenteral administration of arginine improves pregnancyoutcomes in underfed and prolific ewes; and 2) the use of arginine or citrullinemay have important implications for the design of an effective treatment forpreventing or ameliorating IUGR in mammals.