METABOLIC EFFECTS OF ANTIHYPERTENSIVE DRUGS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 代谢综合征患者，其主要特征是胰岛素抵抗，发生糖尿病的风险增加，并经常有高血压-HTN。噻嗪类利尿剂被推荐用于治疗代谢综合征患者的HTN，尽管其与导致胰岛素抵抗增加的代谢紊乱相关。本研究的主要假设是，在代谢综合征和HTN患者中，用血管紧张素转换酶-ACE抑制剂阻断肾素-血管紧张素系统-RAS可减弱噻嗪类利尿剂的不良代谢作用。具体的目的是调查是否发生这种衰减后，加入ACE抑制剂利尿剂和/或作为一个ACE抑制剂预处理的结果。 此外，将在一个单独的6000例高血压CAD患者队列中进行基于实验室的药物基因组学研究，以确定ACE、ADD 1和KCNJ 1基因中与糖尿病相关的多态性，这些基因是根据其在ACE抑制剂和利尿反应中的关键作用选择的。这项研究旨在克服关于代谢综合征患者抗高血压药物代谢影响的知识空白，并将提供影响未来处方模式的数据。

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. Patients with metabolic syndrome, characterized primarily by insulin resistance are at increased risk of developing diabetes and often have hypertension-HTN. Thiazide diuretics are recommended for treating HTN in patients with metabolic syndrome, despite being associated with metabolic disturbances that result in increased insulin resistance. The major hypothesis of this study is that in patients with metabolic syndrome and HTN, blockade of the renin-angiotensin system-RAS with an angiotensin converting enzyme-ACE inhibitor attenuates the adverse metabolic effects of a thiazide diuretic. Specific aims are designed to investigate whether this attenuation occurs after the addition of ACE inhibitor to diuretic and/or as a consequence of pretreatment with an ACE inhibitor. Also, laboratory based pharmacogenomic investigations will be conducted in a separate cohort of 6000 hypertensive CAD patients to identify polymorphisms associated with diabetes in the ACE, ADD1 and KCNJ1 genes, selected on the basis of their critical role in ACE inhibitor and diuretic response. This research seeks to overcome gaps in knowledge regarding the metabolic impact of antihypertensive drugs in patients with metabolic syndrome and will provide data to influence future prescribing patterns.