EFFECT OF PREGNANCY UPON ENDOTHELIAL FUNCTION

内皮调节血管平滑肌对内源性 通过代谢使它们失活或通过 释放其自身的血管活性剂。 通常情况下，有一个微妙的 扩张器和收缩器之间的平衡。 这种平衡在某些情况下会失去。 疾病状态。 关于怀孕对胎儿的影响， 内皮功能 怀孕与减少 对许多内源性收缩物的敏感性，血管收缩减少， 阻力和增加的心输出量的再分布。 的 直接导致这些改变的刺激尚不清楚， 不知道他们是否有联系。 怀孕与增加 子宫动脉内皮舒张因子（EDRF）。 的 子宫动脉对去甲肾上腺素的收缩反应降低 妊娠继发于EDRF。 我们假设内皮或生殖重要的血管 怀孕期间床会发生激素变化，从而增强补品 并刺激内皮扩张剂的释放， 收缩肌 我们进一步假设，这些变化是直接 负责母体心输出量向器官的再分配 这对成功怀孕和减少血管紧张素转换酶活性至关重要。 对收缩剂敏感。 具体目的1：确定NO-EDRF释放的时间过程， 内皮机制，介导妊娠期间EDRF的增加。 具体目标2：确定是否紧张或刺激释放的 NO-EDRF依赖于雌激素。 具体目标3：确定增加的ACh-EDRF活性是否 在怀孕期间或雌激素预处理后， 毒蕈碱受体状态 具体目标4：确定妊娠是否对 血管内皮源性血管活性因子在动脉和静脉中不同 从"生殖"和"非生殖"器官。

The endothelium modulates the vascular smooth muscle response to endogenous constrictor substances by either inactivating them metabolically or by releasing its own vasoactive agent(s). Normally, there is a delicate balance between dilators and constrictors. This balance is lost in some disease states. Little is known about the effect of pregnancy upon endothelial function. Pregnancy is associated with a reduction in sensitivity to many endogenous constrictors, a decrease in vascular resistance, and a redistribution of an increased cardiac output. The stimuli directly responsible for these alterations are unclear and it is unknown if they are linked. Pregnancy is associated with increased endothelium derived relaxing factor (EDRF) in the uterine artery. The decreased uterine artery contractile responses to norepinephrine during pregnancy are secondary to EDRF. We hypothesize that the endothelium or reproductively important vascular beds are hormonally altered during pregnancy resulting in enhanced tonic and stimulated release of endothelial dilators and decreased release of constrictors. We further hypothesize that these changes are directly responsible for the redistribution of maternal cardiac output to organs crucial for a successful pregnancy and the reduction in vascular sensitivity to constrictor agents. Specific Aim 1: To determine the time course of NO-EDRF release and endothelial mechanisms which mediate the increase in EDRF during pregnancy. Specific Aim 2: To determine whether the tonic or stimulated release of NO-EDRF is estrogen dependent. Specific Aim 3: To determine whether the increased ACh-EDRF activity during pregnancy or after estrogen pretreatment parallels a change in muscarinic receptor status. Specific Aim 4: To determine whether the effect of pregnancy upon endothelium-derived vasoactive factors differs among arteries and veins from "reproductive" and "nonreproductive" organs.