Blood Pressure Control by CYP3A Enzymes

描述（由申请人提供）：我提出的研究目标是研究细胞色素P450 3A （CYP3A）酶在调节血压中的作用。该项目源于先前在模型动物和人类中CYP3A活性与某些高血压状态的关联。因此，我建议研究小鼠模型中的血压和细胞培养中的报告基因对内源性和转基因CYP3A酶操作的反应。我推测CYP3A活性的增加会导致血压升高和电解质平衡的改变，包括钠潴留的增加。我会用尾部袖带血压计和遥测技术测量基因操作的效果。由于CYP3As也是药物代谢酶，我所建立的模型也可能对其他研究者的药理学研究有用。我的研究所带来的主要潜在好处将是确定一个多态和潜在可修改的靶标，对控制人类血压和心血管疾病死亡风险有重大影响。

DESCRIPTION (provided by applicant): The goal of my proposed research is to investigate the role of cytochrome P450 3A (CYP3A) enzymes in the regulation of blood pressure. This project stems from previous associations of CYP3A activity with certain hypertensive states in model animals and in humans. I thus propose to study the response of blood pressure in mouse models and of reporter genes in cell cultures to manipulations of endogenous and transgenic CYP3A enzymes. I hypothesize that increased CYP3A activity will result in increased blood pressure and alterations in electrolyte balance that include an increase in sodium retention. I will measure the effects of genetic manipulations with tail cuff sphygmomanometry and telemetry. As the CYP3As are also drug metabolizing enzymes, the models that I generate may also be useful for pharmacology studies by other investigators. The major potential benefit conferred by my research would be the identification of a polymorphic and potentially modifiable target with major effects upon the control of human blood pressure and the risk of cardiovascular disease death.