Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

• 批准号: 2415584
• 负责人: DANIEL L ELY
• 金额: $ 25.81万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415584
• 关键词: androgen receptor; autosomal recessive trait; biomarker; dietary sodium; familial hypertension; genetic strain; histogenesis; kidney metabolism; male; molecular cloning; norepinephrine; renin angiotensin system; sex linked trait; spontaneous hypertensive rat; stress proteins; sulfatases; sympathetic nervous system; testicular feminization; testosterone

The long term objectives of this application are to understand the mechanisms by which the Y chromosome from spontaneously hypertensive rats (SHR) produces a significant blood pressure rise. The Y chromosome blood pressure effect has now been documented in two other independent laboratories but the genetic and physiological mechanisms are not known. There appears to be both sympathetic nervous system (SNS) and androgen components to the Y mediated blood pressure effect. This research will benefit our understanding of one of the genetic components of hypertension and parallels what is observed in human populations. The specific aims will focus on: l) how the SNS may influence testicular development, vascular reactivity and renal metabolism of norepinephrine, 2) if gonadotropin releasing hormone may be released early due to the Y chromosome, 3) if the Y chromosome enhances salt sensitivity, 4) identification and cloning of the heat shock protein sequence on the Y chromosome and 5) determination of the mechanism of the Y chromosome influence on steroid sulfatase in specific tissues. These aims will be accomplished by using both physiological, genetic and molecular techniques. Blood pressure will be measured by telemetry in several studies throughout' the prepubertal and pubertal stages during which blood pressure rapidly rises. molecular studies measuring components of the renin angiotensin system in testes and kidney will be examined and heat shock protein expression will be determined in relevant target organs, such as, aorta, resistance 'vessels, kidney, heart and adrenal glands. Biochemical measurements of indices of the SNS will evaluate the mechanism of elevated adrenergic responsiveness (increased norepinephrine content, release, turnover) in target' organs influencing blood pressure. in some experiments the genetically testicular feminized male will be studied to determine the interaction of the Y chromosome, androgens, androgen receptor and the SNS upon blood pressure. The results of these studies should enhance our understanding of the mechanism of the Y chromosome effect upon blood pressure.

本应用程序的长期目标是了解 自发性高血压大鼠Y染色体的机制 （SHR）产生显着的血压升高。 Y染色体血液 现在已经在另外两个独立中记录了压力效应 实验室，但遗传和生理机制尚不清楚。 似乎有交感神经系统（SNS）和雄激素 Y介导的血压效应的成分。 这项研究会 有益于我们对高血压的遗传成分之一的理解 并平行人口中观察到的内容。具体目标 将重点关注：l）SNS如何影响睾丸发育， 去甲肾上腺素的血管反应性和肾脏代谢，2）如果 由于Y，促性腺激素释放激素可能会提早发布 染色体，3）如果Y染色体增强了盐敏感性，则为4） y上热激蛋白序列的鉴定和克隆 染色体和5）确定Y染色体机理 对特定组织中类固醇硫酸酶的影响。这些目标将是 通过使用生理，遗传和分子来完成 技术。 血压将通过遥测来测量几个 整个研究期间的研究 压力迅速上升。 分子研究测量的成分 将检查睾丸和肾脏中的肾素血管紧张素系统并加热 电击蛋白表达将在相关目标器官中确定 例如主动脉，抗性的血管，肾脏，心脏和肾上腺。 SNS指数的生化测量结果将评估机制 肾上腺素能反应升高（去甲肾上腺素含量增加， 释放，营业额）在影响血压的目标器官中。在某些人中 实验将研究遗传性睾丸女性男性 确定Y染色体，雄激素，雄激素的相互作用 受体和血压下的SN。 这些研究的结果 应该增强我们对Y染色体机制的理解 对血压的影响。