EFFECT OF GENETIC POLYMORPHISMS IN THE EPOXYGENASE PATHWAY ON SALT EXCRETION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。已知由细胞色素P450途径产生的花生四烯酸代谢产物环氧二十碳三烯酸(EETs)在动物模型中可以抑制肾脏钠再流产，在可能患有盐敏感和/或耐盐高血压的健康受试者中可能具有类似的效果。这种P450途径(环氧合酶途径)的基因多态性可能导致EETS、DHETS和肾脏盐排泄水平的改变，并可能在盐敏感型高血压中发挥机制作用。具体目的1：对高血压患者的环氧合酶途径(CYP2J2、CYP2C8、CYP2C9和sEH)进行基因分型，比较非裔美国人和高加索人群中年龄和种族匹配的对照人群中变异等位基因的频率。具体目的2：确定盐负荷和盐缺乏对非裔美国人和高加索人盐敏感(SS)和耐盐(SR)高血压患者尿液和血浆花生四烯酸代谢产物的影响。具体目的3：确定环氧合酶基因对盐负荷和盐耗竭反应的影响，并将这些影响与SS和SR高血压患者不同亚组的血浆和尿花生四烯酸代谢产物相关联。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Arachidonic acid metabolities generated by the cytochrome P450 pathway, epoxyeicosatrienoic acid (EETs) are known to inhibit renal sodium reaborption in animal models and may have similar effects in healthy human subjects which may be perturbed in salt-sensitive and/or salt-resistent hypertension. Genetic polymorphisms in this P450 Pathway (the epoxygenase pathway) may lead to altered levels of EETs, DHETS and renal salt excretion and may play a mechanistic role in salt-sensitive hypertension. Specific Aim 1: Genotype hypertensive subjects for polymorphisms of the epoxygenase pathway (CYP2J2, CYP2C8, CYP2C9, and sEH) and compare the frequency of variant alleles age and race matched controls in African-American and Caucasian populations. Specific Aim 2: Determine the effect of salt loading and salt depletion on urinary and plasma arachidonic acid metabolites in salt-sensitive (SS) and salt-resistant (SR) hypertension in African-American and Caucasian populations. Specific Aim 3: Determine the effect of epoxygenase genotype on response to salt loading and salt depletion and correlate these effects with plasma and urinary arachidonic acid metabolites in various subgroups in SS and SR hypertension.