CARDIAC RECEPTOR ACTIVITY IN THE PREGNANT RAT

血容量增加和血压下降是早期和持续的 与阳性直接相关的妊娠改变 结果。这些心血管调节的长期维持意味着 自主神经调节通路的显著变化，已知 由这些通路介导的反射效应在大鼠和人类中被减弱 妊娠，并在疾病期间进一步钝化，如先兆子痫。其中之一 我们的长期目标是描述这些神经反射的变化 在妊娠过程中的途径，并阐明涉及的机制。理解 这些心血管调节系统的改变将改善临床 妊娠期的血量和血压管理。利用孕妇 老鼠模型，它经历了与人类相似的血液动力学变化，我们 已经证明自主神经受体中的传入放电，这是 调节血量和血压，在怀孕期间减弱。一 对心脏受体敏感性降低的解释是这样的 怀孕实际上代表了一种“营养不足”的状态，而这个概念 将在本提案中进行探讨。此外，我们正在调查 室壁牵张和局部旁分泌因子改变在高血压病中的作用 妊娠期间传入感受器放电的减少。根据我们的发现 在当前的筹资周期中，为这项竞争提出了三个目标 更新：目标1：我们将确定外源性血容量扩张是否恢复 晚孕大鼠心脏受体活性达到 未怀孕的动物，如果体积扩张在 早孕动物：目的2：右房压力/内径关系 将在怀孕后期和未怀孕的动物身上进行测量，以获得更好的 了解心脏感受器“感觉”到的伸展程度；目标3： 我们将确定一氧化氮和/或内皮素，这些已知的物质 减少非妊娠动物的压力感受器放电，调节 我们在怀孕期间观察到心脏和压力感受器的活动。这个 从逻辑上讲，拟议的研究计划源于研究人员目前资助的 心血管功能自主神经调节的研究进展 怀孕了。在本批款期内收集的数据提供了 关于自主神经受体的妊娠调节的有趣新信息 妊娠大鼠的活动。在这次竞争性更新中，我们将专注于我们的 在这些妊娠变化中涉及的机制的努力。洞察力 从这些研究中获得的信息将扩大对心血管疾病的理解 到目前为止还没有研究过的自主神经调节通路中的控制 怀孕，并将进一步阐明生理以及病理 妊娠期血容量和血压的控制机制 将拓宽我们对孕妇临床管理的知识基础。

Increased blood volume and decreased blood pressure are early and sustained alterations of pregnancy that are directly correlated with positive outcomes. The chronic maintenance of these cardiovascular adjustments implies a significant change in autonomic regulatory pathways, and it is known that reflex effects mediated by these pathways are attenuated during rat and human pregnancy, and further blunted during diseases, such as preeclampsia. One of our long-term objectives is to characterize alterations in these neural reflex pathways during pregnancy and to elucidate mechanisms involved. Understanding changes in these cardiovascular regulatory systems will improve clinical management of blood volume and pressure during pregnancy. Using the pregnant rat model, which undergoes hemodynamic changes similar to those in humans, we have demonstrated that afferent discharge in the autonomic receptors, which regulate blood volume and blood pressure, is attenuated during pregnancy. One explanation for a reduction in cardiac receptor sensitivity is the suggestion that pregnancy actually represents an "underfilled" state, and this concept will be explored in the present proposal. In addition, we are investigating the role of alterations in wall stretch and local paracrine factors in the reduction of afferent receptor firing during pregnancy. Based on our findings in the current funding cycle, three aims are proposed for this competing renewal: Aim #1: we will determine if exogenous blood volume expansion restores cardiac receptor activity in the late-pregnant rat to levels observed in the nonpregnant animal, and if volume expansion has a differential effect in the early-pregnant animal; Aim #2: right atrial pressure/dimension relationships will be measured in late-pregnant and nonpregnant animals to gain a better understanding of the degree of stretch "sensed" by cardiac receptors; Aim #3: we will determine whether nitric oxide and/or endothelin, substances known to decrease baroreceptor firing in nonpregnant animals, mediate the reduction in cardiac and baroreceptor activity we have observed during pregnancy. The proposed research plan stems logically from the investigator's currently funded work on alterations in autonomic regulation of cardiovascular function during pregnancy. Data collected during the current grant period have provided intriguing new information about gestational modulation of autonomic receptor activity in the gravid rat. In this competitive renewal we will focus our efforts on mechanisms involved in these changes of pregnancy. The insights gained from these investigations will extend the understanding cardiovascular control in a heretofore-unstudied component of autonomic regulatory pathways in pregnancy, and will further elucidate physiologic as well and pathologic mechanisms of blood volume and blood pressure control during pregnancy that will broaden our knowledge base for clinical management of the pregnant woman.