Zhao X, Nijland M J, Ervin M G, Ross M G
Department of Obstetrics and Gynecology, University of California Los Angeles School of Medicine, Harbor-UCLA Medical Center, Torrance 90502, USA.
Am J Obstet Gynecol. 1998 Oct;179(4):899-905. doi: 10.1016/s0002-9378(98)70186-3.
Fetal arginine vasopressin contributes to fetal and amniotic fluid homeostasis by increasing water resorption in the kidney and, at higher plasma levels, circulatory homeostasis by vasopressor effects. In utero and neonatal exposure of rat pups to prolonged alterations in plasma osmolality may permanently alter (imprint) pituitary arginine vasopressin content and adult responses to osmotic challenges. Our objective was to investigate fetal developmental changes and the impact of maternal dehydration and maternal hyponatremia on fetal pituitary arginine vasopressin content and hypothalamic arginine vasopressin messenger ribonucleic acid expression.
Ten pregnant ewes with singleton fetuses (135 +/- 1 day) were chronically prepared with maternal vascular catheters. Ewes were assigned to receive water deprivation (n = 4) [desamino, D-Arg8]-arginine vasopressin-induced plasma hyponatremia (n = 3), or 4 days of observation (n = 3). Three additional pregnant ewes with preterm (110 +/- 1 day) singleton fetuses were also included for a study of maturational effects. Daily maternal blood samples were analyzed for determination of plasma arginine vasopressin, electrolytes, and osmolality. After the study protocol, fetuses were operatively delivered, umbilical blood samples obtained, and fetuses put to death for pituitary and hypothalamic tissues. Pituitary arginine vasopressin content was determined by radioimmunoassay, and hypothalamus arginine vasopressin messenger ribonucleic acid expression was detected by Northern blotting.
Dehydration significantly (P < .05) increased, and hyponatremia significantly decreased maternal plasma sodium concentration compared with controls. Fetal plasma sodium concentration significantly changed in parallel with maternal values (dehydration: 139 +/- 1 to 150 +/- 1 mEq/L; hyponatremia: 138 +/- 1 to 128 +/- 5 mEq/L). Fetal hypothalamic arginine vasopressin messenger ribonucleic acid expression and pituitary content did not change in relation to these relatively acute alterations in plasma tonicity. However, among all animals, arginine vasopressin messenger ribonucleic acid expression was significantly negatively correlated with pituitary arginine vasopressin content (r2 = 0.563; P = .02). Arginine vasopressin messenger ribonucleic acid expression was significantly lower in both preterm and near-term fetuses (P < .05) than that in the maternal ewe, although pituitary arginine vasopressin content (in micrograms per milligram of protein) was significantly greater in preterm fetuses (P < .01, vs maternal; P < .05, vs near term).
The significant inverse relation between arginine vasopressin content and arginine vasopressin messenger ribonucleic acid suggests a dynamic arginine vasopressin synthesis-content feedback relationship is functional in the near-term fetus. Although relatively acute periods of maternal hypertonicity or hypotonicity do not alter fetal pituitary arginine vasopressin content or hypothalamic arginine vasopressin messenger ribonucleic acid expression, longer-term plasma tonicity alterations may potentially have an impact on the fetal arginine vasopressin hypothalamic-pituitary axis.
胎儿精氨酸加压素通过增加肾脏对水的重吸收来维持胎儿和羊水的内环境稳定，在血浆水平较高时，还可通过升压作用维持循环系统的内环境稳定。大鼠幼崽在子宫内和新生儿期暴露于血浆渗透压的长期改变中，可能会永久性地改变（印记）垂体精氨酸加压素的含量以及成年后对渗透压挑战的反应。我们的目的是研究胎儿发育过程中的变化，以及母体脱水和母体低钠血症对胎儿垂体精氨酸加压素含量和下丘脑精氨酸加压素信使核糖核酸表达的影响。
对10只怀有单胎胎儿（135±1天）的怀孕母羊进行长期准备，在其母体血管中置入导管。将母羊分为三组，分别接受禁水（n = 4）、[去氨基，D-精氨酸8]-精氨酸加压素诱导的血浆低钠血症（n = 3）或观察4天（n = 3）。另外纳入3只怀有早产单胎胎儿（110±1天）的怀孕母羊，用于研究成熟效应。每天采集母体血液样本，分析血浆精氨酸加压素、电解质和渗透压。研究方案结束后，通过手术取出胎儿，采集脐血样本，然后处死胎儿以获取垂体和下丘脑组织。通过放射免疫分析法测定垂体精氨酸加压素含量，通过Northern印迹法检测下丘脑精氨酸加压素信使核糖核酸表达。
与对照组相比，脱水显著（P <.05）增加了母体血浆钠浓度，而低钠血症则显著降低了母体血浆钠浓度。胎儿血浆钠浓度与母体值平行显著变化（脱水：139±1至150±1 mEq/L；低钠血症：138±1至128±5 mEq/L）。胎儿下丘脑精氨酸加压素信使核糖核酸表达和垂体含量并未因这些血浆张力的相对急性改变而发生变化。然而，在所有动物中，精氨酸加压素信使核糖核酸表达与垂体精氨酸加压素含量显著负相关（r2 = 0.563；P =.02）。早产和足月胎儿的精氨酸加压素信使核糖核酸表达均显著低于母羊（P <.05），尽管早产胎儿垂体精氨酸加压素含量（每毫克蛋白质中的微克数）显著高于母羊（P <.01，与母羊相比；P <.05，与足月胎儿相比）。
精氨酸加压素含量与精氨酸加压素信使核糖核酸之间的显著负相关表明，动态的精氨酸加压素合成-含量反馈关系在足月胎儿中发挥作用。尽管母体高渗或低渗的相对急性期不会改变胎儿垂体精氨酸加压素含量或下丘脑精氨酸加压素信使核糖核酸表达，但长期的血浆张力改变可能会对胎儿精氨酸加压素下丘脑-垂体轴产生影响。
