PATHOGENESIS OF SPONTANEOUS HYPERTENSION

自发性高血压大鼠(SHR)是目前研究最广泛的高血压动物模型。这种菌株，像许多患有高血压的人一样，表现出胰岛素抵抗和血脂异常，以及血压升高。然而，主要机制我们发现，将正常血压的Brown挪威(BN)大鼠的一段4号染色体转移到SHR的遗传背景上可以改善SHR的胰岛素敏感性、血脂水平和血压(BP)，改善SHR-CRR4同源品系的胰岛素敏感性、血脂水平和血压(BP)。编码脂肪酸转运蛋白的CD36基因的缺失被发现是与4号染色体这个区域相关的脂肪酸/脂肪代谢的SHR缺陷的原因。然而，分子和生理学研究表明，CD36的突变形式可能不是该染色体区域对血压和胰岛素抵抗影响的原因。在目前的研究中，我们建议衍生和表型多个重组同源基因亚系，从基因上剖析胰岛素抵抗与高血压的关联，并进一步研究该模型中多个心血管的聚集性。

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.