PATHOGENESIS OF SPONTANEOUS HYPERTENSION

自发性高血压大鼠（SHR）是研究最广泛的高血压动物模型。像许多患有原发性高血压的人一样，这种菌株表现出胰岛素抵抗和血脂异常以及血压升高。我们发现，将正常血压的褐挪威（BN）大鼠的4号染色体片段转移到SHR遗传背景上，可以改善大鼠的胰岛素敏感性、脂质水平和血压（BP），并改善SHR-chr 4基因株的胰岛素敏感性、脂质水平和血压（BP）。编码脂肪酸转运体的Cd36基因的缺失已被发现是导致与4号染色体该区域相关的脂肪酸/脂质代谢SHR缺陷的原因。然而，分子和生理学研究表明，突变形式的Cd36不太可能对该染色体区域对BP和胰岛素抵抗的影响负责。在目前的研究中，我们提出衍生多个重组同源亚群并对其进行表型分析，以从遗传学角度分析胰岛素抵抗与高血压的关系，并进一步研究该模型中多个心血管的聚类。

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.