REGULATION OF VASOPRESSIN RELEASE IN HYPERTENSION

高血压时加压素释放的调节

• 批准号: 3339583
• 负责人: CELIA D SLADEK
• 金额: $ 11.27万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-01-01 至 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3339583
• 关键词: acetylcholine; angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; arginine vasopressin; baroreceptors; brain stem; cardiovascular pharmacology; electrolyte balance; extracellular; hormone regulation /control mechanism; neuroendocrine system; neurons; norepinephrine; renin

Existing evidence suggests that vasopressin (VP, antidiuretic hormone) release is elevated in several types of experimental hypertension as well as in humans with hypertension. Furthermore, the VP system is hyperresponsive to certain stimuli in rats genetically disposed to spontaneous development of hypertension (e.g. the spontaneously hypertensive rats (SHRs) developed by Okamoto) but relationships between this hyperresponsiveness and the hypertension is unclear. Therefore, experiments are proposed to evaluate this relationship. Two approaches will be used: 1). The importance of the hyperresponsiveness to the development of hypertension will be evaluated by chronically blocking the vasopressin effects of VP with an analog of VP which has specific pressor antagonist actions. Similarly the contribution of elevated VP release to the maintenance of blood pressure at the different stages of the hypertensive process will be analyzed by acutely infusing the VP pressor antagonist during the development and chronic phases of hypertension. 2). The opposite relationship also will be examined, e.g. the potential role of the hypertension in initiating the hyperresponsiveness of the VP system or in the eventual disappearance of the hyperresponsiveness. This will be evaluated by using three interventions to prevent development of the hypertension and examining the responsiveness of the VP system in rats with these interventions. The interventions employed will be chronic converting enzyme inhibition, intraventricular 6-hydroxydopamine injections, and renal denervation. In rats maintained normotensive with some of these interventions, the responsiveness of the renin-angiotensin system and the NE innervation of VP neurons also will be evaluated, because abnormalities in these factors have also been observed in SHRs.

现有证据表明加压素（VP，抗利尿激素） 在几种类型的实验性高血压中释放也升高 就像患有高血压的人一样。 此外，VP系统是 遗传倾向的老鼠对某些刺激反应过度 高血压的自发发展（例如自发性高血压） 冈本开发的高血压大鼠（SHR））但之间的关系 这种高反应性和高血压的关系尚不清楚。 所以， 建议进行实验来评估这种关系。 两种方法 将使用： 1）。高反应性对发育的重要性 通过长期阻断加压素来评估高血压 VP 与具有特定升压拮抗剂的 VP 类似物的作用 行动。 同样，VP 释放升高对 高血压不同阶段的血压维持 将通过快速注入 VP 升压拮抗剂来分析过程 在高血压的发展和慢性阶段。 2）。还将检查相反的关系，例如潜力 高血压在引发 VP 高反应性中的作用 系统或最终消失的高反应性。 这 将通过使用三种干预措施来评估，以防止发展 高血压并检查大鼠 VP 系统的反应性 通过这些干预措施。 所采用的干预措施将是长期的 转换酶抑制，心室内 6-羟基多巴胺 注射和肾去神经术。 在维持正常血压的大鼠中 其中一些干预措施，肾素-血管紧张素的反应性 系统和 VP 神经元的 NE 神经支配也将被评估，因为 在 SHR 中也观察到这些因素的异常。