Imprint Osmoregulation/Maternally-Dehydrated Offspring

印记渗透调节/母体脱水后代

• 批准号: 6745152
• 负责人: Mina Desai
• 金额: $ 13.13万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6745152
• 关键词: arginine vasopressin; astrocytes; body fluid osmolarity; body water dehydration; genomic imprinting; hormone biosynthesis; hormone receptor; laboratory rat; pregnancy; receptor binding; receptor expression; tissue /cell culture

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.

描述（由候选人提供）： 妊娠唤起了流体室组成和体积的显着适应性适应。在人类和大鼠怀孕期间，孕产妇血容量增加，血浆渗透压降低。由于过度染色，运动或脱水，无法充分“重置”母体血浆渗透或暴露于孕产妇血浆高渗性，从而导致胎儿血浆渗透压增加，从而刺激胎儿精氨酸加压素（AVP）分泌，从而导致AMNNIOMITICICICICICICICINITICINITICINICICINITICINITICINITICINITICINITICINITICINITICINIORID（AF）体积。相反，诱导的母体血浆低音性减少了胎儿血浆渗透压，增加胎儿尿液的流量，减少胎儿吞咽并增加绵羊和人类的AF体积。更重要的是，子宫血浆补体改变的慢性变化新生大鼠以及人类的渗透调节以及包括AVP合成和分泌的肾脏反应以及可能是血压。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，高血压和冠心病的敏感性。印迹渗透调节可能也可能具有代际作用，因此女性后代可能无法适当地重置其血浆渗透压，并在随后的怀孕期间充分扩大血浆量。我们对大鼠的初步研究表明，怀孕期间的母体脱水会导致新生儿的高钠血症和高渗性。我们假设孕产妇脱水改变了新生儿和成年后代的基础血浆隆起性，这是因为：（1）中央有孔受感受器核的渗透测量较高的固定点，并改变了细胞体积调节或（2）（2）降低了基础AVP mRNA和AVP刺激，以及3个响应（3），及其响应（3），以及（3），或者（3）响应（3）。肾脏抗原。我们建议检查中央和外围机制，以构成AVP - 摩托管制系统的印迹。我们将确定分子和细胞机制和外周肾脏AVP受体的变化。最后，我们将描述AVP/Osmoregulatoration途径的关键时期。