Blood Pressure Control by CYP3A Enzymes

通过 CYP3A 酶控制血压

• 批准号: 7008521
• 负责人: Raymond Carlos Givens
• 金额: $ 2.83万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7008521
• 关键词: blood pressure; cardiovascular disorder diagnosis; cell line; complementary DNA; cytochrome P450; dietary sodium; electrolyte balance; enzyme activity; gene expression; genetic manipulation; genetic models; genetic polymorphism; genetically modified animals; human genetic material tag; hydroxysteroid dehydrogenases; isozymes; laboratory mouse; model design /development; nutrition related tag; predoctoral investigator; reporter genes; telemetry; tissue /cell culture

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.

描述(申请人提供)：我提议的研究目标是调查细胞色素P450 3A(细胞色素P450 3A)酶在调节血压中的作用。该项目源于之前在模型动物和人类中发现的细胞色素P3A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血压的反应以及细胞培养中报告基因对内源性和转基因CYP3A酶的操作的反应。我推测，CYP3A活性增加会导致血压升高和电解质平衡的改变，其中包括钠滞留的增加。我将用尾袖血压计和遥测来测量基因操作的效果。由于CYP3A也是药物代谢酶，我建立的模型也可能对其他研究人员的药理学研究有用。我的研究赋予的主要潜在好处将是确定一个对控制人类血压和心血管疾病死亡风险具有重大影响的多态和潜在可修改的靶点。