PATHOGENESIS OF SPONTANEOUS HYPERTENSION

自发性高血压的发病机制

• 批准号: 6288380
• 负责人: THEODORE W KURTZ
• 金额: $ 3.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-09 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6288380
• 关键词: blood pressure; carbohydrate metabolism; chromosomes; disease /disorder model; disease /disorder proneness /risk; essential hypertension; fatty acid metabolism; genetic mapping; genetic markers; genotype; hyperlipidemia; hypertension; hypertriglyceridemia; hypolipidemia; insulin sensitivity /resistance; mutant; pathologic process; phenotype; quantitative trait loci; spontaneous hypertensive rat

The spontaneously hypertensive rat (SHR) is the most widely studied animal model of high blood pressure. This strain, like many humans with essential hypertension, exhibits insulin resistance and dyslipidemia as well as increased blood pressure. However, the primary mechanisms We found that transferring a piece of chromosome 4 form the normotensive Brown Norway (BN) rat onto the genetic background of the SHR improves insulin sensitivity, lipid levels, and blood pressure (BP) rat onto the genetic background of the SHR improves insulin sensitivity, lipid levels, and blood pressure (BP) in the SHR-chr 4 congenic strain. A deletion in the Cd36 gene that encodes a fatty acid transporter has been found to be responsible for the SHR defects in fatty acid/lipid metabolism associated with this region of chromosome 4. However, molecular and physiologic studies indicate that the mutant form of Cd36 is not likely to be responsible for the effect of this chromosome region on BP and insulin resistance. In the current studies, we propose to derived and phenotype multiple recombinant congenic sublines to genetically dissect the association of insulin resistance and hypertension and further investigate the clustering of multiple cardiovascular in this model.

自发性高血压大鼠（SHR）是研究最广泛的高血压动物模型。这种菌株像许多具有必要高血压的人一样，表现出胰岛素抵抗和血脂异常以及血压升高。 However, the primary mechanisms We found that transferring a piece of chromosome 4 form the normotensive Brown Norway (BN) rat onto the genetic background of the SHR improves insulin sensitivity, lipid levels, and blood pressure (BP) rat onto the genetic background of the SHR improves insulin sensitivity, lipid levels, and blood pressure (BP) in the SHR-chr 4 congenic strain.已发现编码脂肪酸转运蛋白的CD36基因的缺失是导致与脂肪酸/脂质代谢相关的SHR缺陷，但分子和生理研究表明，CD36的突变体形式不可能负责该Chromosome对BP和Inston bp and的影响。在当前的研究中，我们建议衍生和表型多重重组先天性额定额定额，以遗传剖析胰岛素抵抗和高血压的关联，并进一步研究该模型中多重心血管的聚类。