Y CHROMOSOME AND HYPERTENSION

该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) 会导致血压显着升高。 Y染色体血液 压力效应现已在另外两个独立的文献中得到记录 实验室，但遗传和生理机制尚不清楚。 似乎同时存在交感神经系统 (SNS) 和雄激素 成分对Y介导的血压作用。 这项研究将 有助于我们了解高血压的遗传成分之一 并与在人群中观察到的情况相似。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 促性腺激素释放激素可能由于 Y 提前释放 染色体，3) 如果 Y 染色体增强盐敏感性，4) Y上热休克蛋白序列的鉴定和克隆 5）Y染色体作用机制的测定 对特定组织中类固醇硫酸酯酶的影响。这些目标将是 通过利用生理、遗传和分子来实现 技术。 血压将通过遥测技术在几个地方进行测量 研究整个青春期前和青春期阶段，在此期间血液 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 将确定相关靶器官中的休克蛋白表达， 例如，主动脉、阻力血管、肾、心脏和肾上腺。 SNS 指标的生化测量将评估其机制 肾上腺素能反应性升高（去甲肾上腺素含量增加， 影响血压的目标器官中的释放、周转）。在一些 实验将研究基因睾丸女性化男性 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 应该增强我们对Y染色体机制的理解 对血压的影响。

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.