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: 6619371
• 负责人: DOUGLAS S MARTIN
• 金额: $ 25万
• 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 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6619371
• 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(来自申请表的逐字记录)：我们实验室的最新数据 表明静脉张力在发育阶段是增加的 大鼠自发性高血压。自从年血压升高以来 高血压的初期特征是心脏高度升高。 输出，静脉似乎在启动的重要作用 高血压过程。高血压的发展是性二态的。 相当多的证据表明，雌激素可以抑制卵巢癌的发展。 高血压。雌激素已被证明通过两种途径影响血管平滑肌 内皮依赖和独立的机制，并调节外周和 中枢神经系统功能。静脉拥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。 高血压的分期通过对静脉平滑肌的影响和/或通过效应 交感神经流出到静脉。因此，拟议的研究旨在 检验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 研究的重点将是确定雌激素是否会降低交感神经 年轻女性自发性高血压患者的静脉收缩音。二)雌激素通过以下途径降低静脉张力 通过对一氧化氮的影响影响静脉平滑肌的反应性 氧化系统、钙通道或钾通道。三)雌激素改变 参与静脉张力控制的关键蛋白的表达。实验 将在6-10周的自发性高血压(SHR)大鼠身上进行 年龄，以前的研究表明自发性高血压患者静脉张力升高的时间点 老鼠。MAP、HR和平均循环充盈压，一个综合的指标 将在清醒的大鼠身上测量毒液运动强度，以确定 雌激素对整体静脉张力的影响。孤立的门静脉和肠系膜静脉将 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。西方印迹技术将是 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 雌激素通过减少毒液运动延缓高血压的发展 基调，从而减少了导致增加的一个主要因素 启动高血压过程的心输出量和血压。