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。与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。然而，其主要机制我们发现，将来自血压正常的布朗挪威（BN）大鼠的一段4号染色体转移到SHR的遗传背景中，改善了SHR-chr 4同源品系中的胰岛素敏感性、脂质水平和血压（BP）大鼠的胰岛素敏感性、脂质水平和血压（BP）。已发现编码脂肪酸转运蛋白的Cd 36基因中的缺失负责与4号染色体的该区域相关的脂肪酸/脂质代谢中的SHR缺陷。然而，分子和生理学研究表明，突变形式的镉36是不可能负责的影响，该染色体区域的BP和胰岛素抵抗。在目前的研究中，我们建议衍生和表型多个重组同源亚系，从遗传上剖析胰岛素抵抗和高血压的关联，并进一步研究在这个模型中的多个心血管聚集。

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.