Estrogen and sodium modulate hypertension in aging rats

雌激素和钠调节衰老大鼠的高血压

• 批准号: 6423696
• 负责人: CARMEN HINOJOSA-LABORDE
• 金额: $ 26.76万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6423696
• 关键词: age difference; angiotensin /renin /aldosterone hypertension; animal old age; cardiovascular disorder chemotherapy; disease /disorder model; estrogens; female; genetic strain; hormone therapy; hypertension; laboratory rat; low salt diet; nitric oxide; nonhuman therapy evaluation; nutrition related tag; ovariectomy; renin angiotensin system; salt intake

DESCRIPTION (provided by applicant): The Dahl salt sensitive (S) rat will be studied as an animal model of post-menopausal hypertension to investigate the mechanisms responsible for the hypertension. The pressor systems that will be evaluated are the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS). The role of estrogen, aging, and salt intake as modulators of these pressor systems via their effects on the nitric oxide (NO) system will be investigated. The first specific hypothesis is that the aging process with the accompanying loss of estrogen activity is associated with a down regulation of the nitric oxide system resulting in hypertension. To test this hypothesis, Specific Aim 1 of this study is to monitor blood pressure and the level of activation of the NO system in intact, ovariectomized (OVX), and OVX+estrogen-treated Dahl salt sensitive and Dahl salt-resistant (R) female rats as they age from 3 month to 20-22 months of age. The second specific hypothesis is that the factors maintaining the hypertension associated with the loss of estrogen activity in Dahl S rats is determined by the level of salt intake. OVX performed at young, middle and old age will cause an increase in blood pressure, but the rise will be attenuated with increasing age. However, the level of blood pressure and the activity of the pressor systems contributing to hypertension will be higher pre-OVX because of the effects of aging on the RAS and SNS. Two specific aims will address this hypothesis. Specific Aim 2 will be to establish that the Dahl S elderly and OVX females maintained on low salt intake will become hypertensive as a result of an activation of the RAS. Estrogen administration will maintain activation of the NO system to suppress the RAS. Blockade of NO formation in low salt animals will increase RAS function, especially in the OVX+estrogen animals. Specific Aim 3 is to determine that high salt fed Dahl S elderly and OVX animals will develop a hypertension that is dependent on the activation of the SNS. As with the low salt animals, estrogen supplement will suppress the SNS stimulation through a NO-mediated mechanism. Together these studies will provide evidence that the arterial pressure of the Dahl S rat is sensitive to the removal of estrogen through OVX or aging suggesting a useful model of post-menopausal hypertension. By investigating the relationship of estrogen, NO and salt, important new information will be gained in the mechanisms whereby estrogen provides protection against hypertension. Importantly, a greater understanding will be obtained addressing why the protection disappears with the aging process.

描述（由申请人提供）：Dahl盐敏感的大鼠将是 作为绝经后高血压的动物模型研究，以研究 负责高血压的机制。将是施加系统 评估是肾素 - 血管紧张素系统（RAS）和交感神经 系统（SNS）。雌激素，衰老和盐摄入量作为调节剂的作用 这些施加系统通过其对一氧化氮（NO）系统的影响 调查。第一个特定的假设是与 伴随雌激素活性的丧失与下调有关 一氧化氮系统导致高血压。为了检验这一假设， 本研究的具体目的1是监测血压和 在完整，卵巢切除（OVX）和 OVX+经雌激素治疗的Dahl盐敏感和抗Dahl盐（R）女性 大鼠年龄从3个月到20-22个月大。第二个特定 假设是维持与 Dahl S大鼠中雌激素活性的损失取决于盐的水平 进气。 OVX在年轻，中年和老年表演将导致增加 血压，但随着年龄的增长，上升将减弱。然而， 血压水平和压力系统的活性 导致高血压的贡献将是较高的前VOVX，因为 在RAS和SNS上衰老。两个具体的目标将解决这一假设。 具体目标2是确定达尔的老年女性 在低盐摄入量中保持的，由于 RAS的激活。雌激素给药将保持 没有系统来抑制RAS。低盐动物中无构造的封锁 将增加RAS功能，尤其是在OVX+雌激素动物中。具体的 AIM 3是确定高盐喂养Dahl的老年人和OVX动物 开发一种取决于SNS激活的高血压。和 低盐动物，雌激素补充剂会抑制SNS刺激 通过无介导的机制。这些研究将提供证据 Dahl S大鼠的动脉压对去除的敏感 通过OVX或衰老的雌激素表明了绝经后的有用模型 高血压。通过研究雌激素，无和盐的关系， 重要的新信息将在雌激素的机制中获得 提供防止高血压的保护。重要的是，有了更大的理解 将获得解决为什么保护随着衰老而消失的原因 过程。