Y CHROMOSOME AND HYPERTENSION

Y 染色体与高血压

• 批准号: 3367198
• 负责人: DANIEL L ELY
• 金额: $ 22.88万
• 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 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3367198
• 关键词: autosomal recessive trait; familial hypertension; genetic strain; hormone receptor; salts; sex linked trait; spontaneous hypertensive rat; stress; sympathetic nervous system

Our recent studies have shown that a primary genetic component of hypertension in the spontaneously hypertensive rat (SHR) is on the Y chromosome. We have developed two new, unique F12 substrains of SHR designated SHR/y and SHR/a, which allow the manipulation of the effects of the Y chromosome. The SHR/y substrain contains a hypertensive Y chromosome in a normotensive autosomal background. The SHR/a substrain contains a normotensive Y chromosome in a hypertensive autosomal background. The hypothesis of this study is that the sympathetic nervous system and the testes interact to produce an elevated blood pressure that is sex linked and one component is ont he Y chromosome. To accomplish this we will: 1) determine the impact of the Y chromosome on sympathetic nervous system responsiveness and the testes, and 2) determine the genetic interaction of the Y chromosome in hypertensive and normotensive genetic backgrounds. Preliminary data suggests that the sympathetic nervous system (SNS) is modulated by the hypertensive Y chromosome. By comparing central and peripheral SNS indicators, steroid profiles, salt sensitivity and salt appetite in the SHR/y and SHR/a substrains we will determine which of these parameters are influenced by the Y chromosome. Based on our results of backcross progeny, the dominant/recessive relationship of the SHR and WKY hypertensive autosomal genes is modified by the Y chromosome. Crosses between the SHR/y and SHR/a substrains and SHR and WKY will be used to investigate this interaction. Finally, matings of our SHR/y substrain to other normotensive inbred rat strains will be used to determine the effect of the hypertensive Y chromosome in other genetic backgrounds to discover modifier loci.

我们最近的研究表明，一个主要的遗传成分