ESTROGEN REDUCES VENOUS TONE IN EARLY HYPERTENSION

雌激素可降低早期高血压的静脉张力

• 批准号: 6193757
• 负责人: DOUGLAS S MARTIN
• 金额: $ 21.08万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6193757
• 关键词: estrogens; female; hormone regulation /control mechanism; hypertension; pathologic process; spontaneous hypertensive rat; vasomotion; western blottings

DESCRIPTION (Verbatim from the application): Recent data from our laboratory indicated that venous tone is increased in the developmental stages of spontaneous hypertension in the rat. Since the increase in blood pressure in the initial stages of hypertension is characterized by an elevation of cardiac output, veins appear to play an important role in the initiation of the hypertensive process. The development of hypertension is sexually dimorphic. Considerable evidence suggests that estrogen attenuates the development of hypertension. Estrogen has been shown to affect vascular smooth muscle via both endothelial dependent and independent mechanisms and to modulate peripheral and central nervous system function. Veins possess functional estrogen receptors, high estrogen states are associated with changes in venous tone and estrogen modulates neural activity in brain regions involved in the control of venous tone. Thus, estrogen may modulate venoconstrictor tone during the developmental stages of hypertension via effects on venous smooth muscle and/or via effects on sympathetic outflow to veins. Accordingly, the proposed research is aimed at testing the general hypothesis that estrogen reduces venoconstrictor tone during the developmental stages of spontaneous hypertension. The specific aims of the research will be to determine if I) Estrogen reduces sympathetic venoconstrictor tone in young female SHR. II) Estrogen reduces venous tone via effects on venous smooth muscle responsiveness via an effect on the nitric oxide system, calcium channels or potassium channels. III) Estrogen alters the expression of key proteins involved in the control of venous tone. Experiments will be performed in spontaneously hypertensive (SHR) rats at 6-10 weeks of age, a time point when previous studies have shown elevated venous tone in SHR rats. MAP, HR, and mean circulatory filling pressure, an index of integrated venomotor tone will be measured in conscious rats to determine the effects of estrogen on overall venous tone. Isolated portal and mesenteric veins will be used to assess the effects of estrogen on venous smooth muscle responsiveness and the mechanisms underlying these effects. Western blot techniques will be used to determine if estrogen affects venous tone by altering expression of key protein involved in venous control systems. These studies are expected to show that estrogen attenuates the development of hypertension by reducing venomotor tone and thereby, reduces a major factor contributing to the increase in cardiac output and blood pressure that initiates the hypertensive process.

描述（来自应用程序的逐字记录）：来自我们实验室的最新数据 表明静脉张力在发育阶段增加， 大鼠自发性高血压。自从1999年血压升高以来， 高血压的初始阶段的特征在于心脏的升高， 输出，静脉似乎发挥了重要作用，在启动 高血压过程高血压的发展具有性别二态性。 相当多的证据表明，雌激素减弱的发展， 高血压雌激素已被证明通过两种途径影响血管平滑肌 内皮依赖性和非内皮依赖性机制，并调节外周和 中枢神经系统功能静脉具有功能性雌激素受体， 高雌激素状态与静脉张力和雌激素的变化有关 调节参与静脉控制的大脑区域的神经活动 语气因此，雌激素可能在发育过程中调节静脉收缩张力， 通过对静脉平滑肌的影响和/或通过对 交感神经流向静脉因此，拟议的研究旨在 验证雌激素降低静脉收缩张力的一般假设 在自发性高血压的发展阶段。具体目标 这项研究的目的是确定I）雌激素是否会降低交感神经系统的功能， 年轻雌性SHR的静脉收缩张力。II）雌激素通过以下途径降低静脉张力 通过影响一氧化氮对静脉平滑肌反应性的影响 氧化物系统、钙通道或钾通道。三）雌激素改变 参与控制静脉张力的关键蛋白质的表达。实验 将在6-10周的自发性高血压（SHR）大鼠中进行 年龄，以前的研究表明SHR静脉张力升高的时间点 大鼠MAP、HR和平均循环充盈压，一个综合指标 将在清醒的大鼠中测量静脉张力以确定 雌激素对整体静脉张力的影响将分离门静脉和肠系膜静脉 用于评估雌激素对静脉平滑肌反应性的影响 以及这些效应背后的机制。蛋白质印迹技术将是 用于确定雌激素是否通过改变key的表达来影响静脉张力 参与静脉控制系统的蛋白质。这些研究预计将显示， 雌激素通过降低血压降低高血压的发展， 因此，减少了一个主要因素，有助于增加 心输出量和血压，引发高血压过程。