Imprint Osmoregulation/Maternally-Dehydrated Offspring

描述(由候选人提供)： 妊娠引起液体间隔的成分和体积发生明显的生理适应。在人和大鼠怀孕期间，母体血容量增加，血浆渗透压降低。由于呕吐、运动或脱水而未能充分“重置”孕妇血浆渗透压或暴露于孕妇血浆高渗状态，会导致胎儿血浆渗透压升高，从而刺激胎儿精氨酸加压素(AVP)分泌，导致羊水(AF)量减少。相反，在羊和人中，诱导的母体血浆低渗降低胎儿血浆渗透压，增加胎儿尿流量，减少胎儿吞咽，增加房颤量。更重要的是，子宫内慢性血浆张力改变会影响新生大鼠和人类的渗透调节和肾脏反应，包括AVP的合成和分泌，可能还会影响血压。渗透调节的印记可能会增加新生儿和/或成人对水/电解质失衡、高血压和冠心病的易感性。也有可能的是，印迹渗透调节可能具有代际影响，使得雌性后代在随后的怀孕期间可能不会适当地重置其血浆渗透压并适当地扩大其血浆容量。我们对大鼠的初步研究表明，怀孕期间母亲脱水会导致新生儿高钠血症和高张血症。我们假设，母体脱水改变了新生儿和成年后代的基础血浆张力，其结果是：(1)中枢渗透压受体核渗透压调节点升高，改变了细胞体积调节，或(2)基础AVP mRNA和合成减少，以及AVP对渗透压刺激的分泌减少，和/或(3)AVP诱导的肾脏抗利尿作用减少。我们建议研究AVP渗透调节系统印迹的中枢和外周机制。我们将确定其分子和细胞机制(S)和外周肾血管加压素受体的变化。最后，我们将描述AVP/渗透调节途径印迹发生的关键时期。

DESCRIPTION (provided by candidate): Pregnancy evokes marked physiologic adaptations in the composition and volume of fluid compartments. During human and rat pregnancy, maternal blood volume increases and plasma osmolality decreases. Failure to adequately "reset" maternal plasma osmolality or exposure to maternal plasma hypertonicity, as a result of hyperemesis, exercise or dehydration, results in increased fetal plasma osmolality, which stimulates fetal arginine vasopressin (AVP) secretion, causing reduced amniotic fluid (AF) volume. Conversely, induced maternal plasma hypotonicity reduces fetal plasma osmolality, increases fetal urine flow, reduces fetal swallowing and increases AF volume in sheep and humans. More importantly, chronic in utero plasma tonicity alterations imprint newborn rat and human osmoregulation and renal responses including AVP synthesis and secretion, and possibly blood pressure. The imprinting of osmoregulation may increase the susceptibility of the newborn and/or adult to water/electrolyte imbalance, hypertension and coronary heart disease. It is also possible that the imprinted osmoregulation may have intergenerational effects such that the female offspring may not appropriately reset their plasma osmolality and adequately expand their plasma volume during their subsequent pregnancies. Our preliminary studies of rats indicate that maternal dehydration during pregnancy results in hypernatremia and hypertonicity in the newborn. We hypothesize that maternal dehydration alters basal plasma tonicity in newborn and adult offspring, as a result of: (1) an elevated osmoregulatory set-point of the central osmoreceptor nuclei, and altered cellular volume regulation or (2) reduced basal AVP mRNA and synthesis, and AVP secretion in response to osmotic stimuli, and/or (3) reduced AVP-induced renal antidiuresis. We propose to examine central and peripheral mechanisms for the imprinting of the AVP-osmoregulatory system. We will determine the molecular and cellular mechanism(s) and peripheral renal AVP receptor changes. Finally, we will delineate the critical period during which imprinting of the AVP/osmoregulatory pathway occurs.