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Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

基本信息

批准号：
2910548
负责人：
DANIEL L ELY
金额：
$ 26.8万
依托单位：
UNIVERSITY OF AKRON
依托单位国家：
美国
项目类别：
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

项目摘要

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.

本申请的长期目标是了解自发性高血压大鼠的Y染色体 (SHR)会导致血压显著升高 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。这项研究将有助于我们理解高血压的遗传成分之一与在人类中观察到的情况相似。具体目标将集中在：l）SNS如何影响睾丸发育，血管反应性和去甲肾上腺素的肾代谢，2）如果促性腺激素释放激素可能由于Y 3）如果Y染色体增强盐敏感性，4） Y染色体上热休克蛋白序列的鉴定和克隆染色体和5）确定Y染色体的机制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学、遗传学和分子生物学技术. 血压将通过遥测测量，在青春期前和青春期阶段的研究中，压力迅速上升。分子研究测量的成分检查睾丸和肾脏中的肾素血管紧张素系统，将在相关靶器官中测定休克蛋白表达，如主动脉、阻力血管、肾、心脏和肾上腺。 SNS指标的生化测定将评估其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）在靶器官中影响血压。在一些将对遗传上睾丸女性化的男性进行研究，确定Y染色体，雄激素，雄激素受体和SNS对血压的影响。这些研究的结果应该能增强我们对Y染色体机制的理解对血压的影响

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sodium intake is increased by social stress and the Y chromosome and reduced by clonidine.

社会压力和 Y 染色体会增加钠的摄入量，可乐定会减少钠的摄入量。

DOI：
10.1152/ajpregu.2000.278.2.r407
发表时间：
2000
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Ely,D;Herman,M;Ely,L;Barrett,L;Milsted,A
通讯作者：
Milsted,A

The SHR Y-chromosome increases testosterone and aggression, but decreases serotonin as compared to the WKY Y-chromosome in the rat model.

在大鼠模型中，与 WKY Y 染色体相比，SHR Y 染色体会增加睾酮和攻击性，但会降低血清素。