NHLBI CLINICAL INVESTIGATOR AWARD PROGRAM

该奖项旨在进一步发展研究技能， 个人的长期职业目标是成为一个独立的 研究者在有关领域的体积稳态和高血压， 怀孕 实验，旨在阐明水处理和作用， 在正常和异常妊娠期间， 在M.D.博士的赞助下进行。Lindheimer如下：I. 水代谢：导致妊娠期糖尿病的因素 血浆渗透压（Posm）和AVP分泌和饮水阈值 将被调查。 将检查连续血压和Posm 在整个怀孕期间，以确定是否妊娠减少平均 动脉压可能是导致血压调节改变的原因 同时研究假孕大鼠以确定胎儿胎盘 单位在这些变化中发挥着特殊的作用。 的可能性 肾素-血管紧张素系统、催乳素和内啡肽也参与其中， 通过对未交配动物给予激素进行检查和/或 通过抑制怀孕动物体内的特定激素。 二. 高血压：这些研究旨在研究血管加压素和 怀孕期间控制血压的相关激素系统 在（1）血压正常的Wistar-Kyoto大鼠中，（2）人类的动物模型 原发性高血压，即自发性高血压大鼠，和（3） 人先兆子痫的动物（大鼠）模型。 将进行实验， 测定血管对AVP、血管紧张素II和儿茶酚胺的反应性 此外，每种物质在维持血液中的作用 将通过施用特定的血管内药物来评估压力。 封闭剂 在平行实验中，血压、容量和水平 将在妊娠早期、中期和晚期测量上述激素的水平。 在人体研究中，水处理、AVP分泌、血浆肾素活性和 将在血压正常的妇女和孕妇中比较儿茶酚胺， 使用生理刺激如水负荷的轻度高血压， 限制. 容量稳态、水处理和血压控制 怀孕的原因知之甚少。 目前获得的信息 调查将有助于更好地了解这些现象 并可能改善高血压的临床管理 妊娠并发症。

This award is sought to further develop the research skills of an individual whose long-term career goal is to become an independent investigator in areas related to volume homeostasis and hypertension in pregnancy. Experiments, designed to elucidate water handling and the role of vasopressin (AVP) during both normal and abnormal gestation will be performed under the sponsorship of Dr. M.D. Lindheimer as follows: I. Water Metabolism: The factors responsible for gestational decreases in both plasma osmolality (Posm) and thresholds for AVP secretion and drinking will be investigated. Serial blood pressure and Posm will be examined throughout pregnancy to determine whether the gestational decrement in mean arterial pressure may be responsible for alterations in osmoregulation while pseudopregnant rats will be studied to determine if the fetoplacental unit plays a specific role in these changes. The possibility that the renin-angiotensin system, prolactin and endorphins are involved will also be examined through administration of hormone to virgin animals and/or through inhibition of specific hormones in gravid animals. II. Hypertension: These studies aim to investigate the role of vasopressin and related hormonal systems in the control of blood pressure during pregnancy in (1) normotensive Wistar-Kyoto rats, (2) an animal model of human essential hypertension, i.e. the spontaneously hypertensive rat, and (3) an animal (rat) model of human preeclampsia. Experiments will be performed to determine the vascular reactivity to AVP, angiotensin II and catecholamines and in addition the contribution of each in the maintenance of blood pressure will be assessed through the administration of specific vascular blocking agents. In parallel experiments blood pressure, volume and levels of the above hormones will be measured in early, mid and late gestation. In human studies water handling, AVP secretion, plasma renin activity and catecholamines will be compared in normotensive women and in gravidas with mild hypertension using physiological stimuli such as water loading and restriction. Volume homeostasis, water handling and blood pressure control in pregnancy are poorly understood. Information gained from present investigations will contribute to a better understanding of these phenomena and may lead to improvement in the clinical management of hypertensive disorders complicating gestation.