Blood Pressure Control by CYP3A Enzymes

通过 CYP3A 酶控制血压

• 批准号: 7164406
• 负责人: Raymond Carlos Givens
• 金额: $ 2.48万
• 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 2007-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7164406
• 关键词: 11p; Adrenal Glands; Agreement; Animal Model; Anterior; Blood Pressure; CYP3A5 gene; Cell Line; Cells; Cessation of life; Complementary DNA; Creatinine clearance measurement; Cultured Cells; Duct (organ) structure; Electrolyte Balance; Elements; Enzymes; Excretory function; Gene Expression; Goals; Green Fluorescent Proteins; Human; Hypotension; Inbred SHR Rats; Injection of therapeutic agent; Kidney; Liver; Long Terminal Repeats; Measures; Metabolic; Mineralocorticoids; Mouse Mammary Tumor Virus; Mus; Pharmaceutical Preparations; Pharmacology; Phosphoglycerate Kinase; Physiological; Pituitary Gland; Plasmids; Protein Isoforms; Rattus; Reaction; Reporter Genes; Research; Research Personnel; Response Elements; Role; Signal Transduction; Single Nucleotide Polymorphism; Sodium; Steroids; Tail; Telemetry; Testing; Tissues; Transgenic Mice; Transgenic Organisms; animal data; blood pressure regulation; cardiovascular disorder risk; cytochrome P450 3A; enzyme activity; enzyme model; genetic manipulation; human data; human disease; inhibitor/antagonist; kidney cell; mouse model; promoter; research study; response; stem; urinary

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（由申请人提供）：本研究的目的是研究细胞色素P450 3A（CYP3A）酶在血压调节中的作用。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，我建议研究的血压在小鼠模型和报告基因在细胞培养中的内源性和转基因CYP3A酶的操纵的反应。我假设CYP3A活性增加将导致血压升高和电解质平衡改变，包括钠潴留增加。我将用尾袖血压计和遥测技术来测量基因操作的效果。由于CYP3A也是药物代谢酶，因此我生成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益处将是鉴定一种多态性和潜在可修饰的靶点，其对人类血压控制和心血管疾病死亡风险具有重大影响。