Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

• 批准号: 2702208
• 负责人: DANIEL L ELY
• 金额: $ 26.3万
• 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/2702208
• 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染色体发生机制的研究 (SHR)会使血压显著升高。Y染色体血液 压力效应现在已经在另外两个独立的 但遗传和生理机制尚不清楚。 似乎既有交感神经系统(SNS)又有雄激素 成分以Y为中介的血压效应。这项研究将 有助于我们了解高血压的一种遗传成分 这与在人类群体中观察到的情况相似。具体目标 将关注：L)社交网络可能如何影响睾丸发育， 去甲肾上腺素的血管反应性和肾脏代谢，2)IF 促性腺激素释放激素可能因Y而提前释放 染色体，3)如果Y染色体增强了盐敏感性，4) 黄曲霉热激蛋白序列的鉴定与克隆 染色体和5)Y染色体机制的确定 对特定组织中类固醇硫酸酯酶的影响。这些目标将是 通过使用生理、遗传和分子 技巧。血压将在几个月内通过遥测测量 在整个青春期前和青春期的研究中，血液 压力迅速上升。分子研究测量的成分 睾丸和肾脏的肾素血管紧张素系统将被检查和加热 将测定休克蛋白在相关靶器官中的表达， 例如，主动脉、阻力血管、肾脏、心脏和肾上腺。 SNS指标的生化测定将评估其作用机制 肾上腺素能反应性升高(去甲肾上腺素含量增加， 释放、周转)影响血压的靶器官。在一些地方 基因上睾丸女性化的男性将被研究 确定Y染色体、雄激素、雄激素的相互作用 受体和SNS对血压的影响。这些研究的结果 应该加深我们对Y染色体机制的理解 对血压的影响。