The Role of Signal Transduction Pathways in Hypertension

信号转导途径在高血压中的作用

• 批准号: 7281775
• 负责人: Exazevia M Logan
• 金额: $ 3.01万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281775
• 关键词: 1,2-diacylglycerol; 1-Phosphatidylinositol 3-Kinase; Adaptor Protein Complex 1; Address; Adrenal Glands; Affect; Affinity; Angiotensin II; Angiotensin II Receptor; Angiotensin II Signaling Pathway; Angiotensins; Animal Model; Animals; Apoptosis; Area; Attention; Attenuated; Baroreflex; Binding; Biological; Blood - brain barrier anatomy; Blood Circulation; Blood Pressure; Blood Vessels; Bradycardia; Brain; Brain Stem; Brain region; Cardiac; Cardiopulmonary; Cardiovascular Physiology; Cardiovascular system; Catecholamines; Cell Nucleus; Cell membrane; Cells; Characteristics; Chemoreceptors; Chronic; Chymosin; Comparative Study; Complex; Conscious; Deposition; Depressed mood; Development; Diglycerides; Disease; Disease Progression; Dopamine; Dorsal; Dose; Environmental Risk Factor; Enzymes; Epidermal Growth Factor; Essential Hypertension; Etiology; Event; Exhibits; Extracellular Matrix; Fellowship; Fiber; Fingerprint; Functional disorder; G-Protein-Coupled Receptors; GTP Binding; GTP-Binding Proteins; Genes; Genetic; Genetic Models; Genetic Predisposition to Disease; Genetic Transcription; Goals; Growth; Hand; Heart; Heart Rate; High Blood Pressure; Homeostasis; Hormones; Hour; Human; Hydrolysis; Hypertension; Hypothalamic structure; In Vitro; Inbred SHR Rats; Inbred WKY Rats; Individual; Inflammation; Inositol; Intake; Investigation; Isoenzymes; Kidney; Knowledge; Laboratories; Lead; Link; Liquid substance; MAPK14 gene; Maintenance; Marshal; Medial; Mediating; Medulla Oblongata; Metabolic; Microinjections; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Mixed Function Oxygenases; Modeling; Morbidity - disease rate; Mus; Names; Neonatal; Nerve; Neuraxis; Neurons; Neurotransmitters; Norepinephrine; Nucleus solitarius; Numbers; Output; PIK3CG gene; Partner in relationship; Pathogenesis; Pathway interactions; Patients; Pattern; Peptides; Peripheral; Pharmaceutical Preparations; Pharmacological Treatment; Phenotype; Phosphatidylinositols; Phospholipase C; Phosphorylation; Phosphotransferases; Physiological; Play; Predisposition; Preparation; Pressoreceptors; Process; Production; Protein-Serine-Threonine Kinases; Ras/Raf; Rattus; Receptor, Angiotensin, Type 1; Regulation; Renal function; Renin; Renin-Angiotensin System; Reporting; Research; Research Design; Role; Series; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Site; Sprague-Dawley Rats; Stimulus; Structure of area postrema; Sympathetic Nervous System; System; Threonine; Tissues; Transgenic Model; Transgenic Organisms; Tyrosine 3-Monooxygenase; Tyrosine Phosphorylation; Validation; Variant; Vascular Smooth Muscle; Vasoconstrictor Agents; Vasomotor; Vasopressins; Yang; arteriole; attenuation; authority; base; blood pressure regulation; brain tissue; cell growth; concept; cytokine; density; falls; granulocyte; in vivo; insight; interest; kinase inhibitor; migration; monocyte colony stimulating factor; mortality; noradrenaline transporter; normotensive; pressure; prevent; protein protein interaction; raf Kinases; receptor; response; rodent genome; sensory neuron specific sodium channel; stress activated protein kinase; tool; vasoconstriction; wortmannin; zygote

DESCRIPTION (provided by applicant): The goal of the planned research is to either confirm or refute the presence of separate phosphatidylinositol 3 (PI3) and mitogen-activated protein (MAP) kinase pathways in the nucleus tract solitarius (NTS) in various models of hypertension. The overall objective is to investigate the signaling mechanisms at this brain site potentially contributing to development and maintenance of sustained hypertension. Our ongoing studies are designed to provide initial information about the relationship between the apparent enhancement of the sympathetic nervous system in various forms of hypertension and the role of PI3 and MAP kinase signaling pathways in the maintenance of hypertension. Our initial goal is to demonstrate that PI3 and MAP kinase signaling pathways in the NTS of (mRen-2)27 transgenic rats are activated in response to Ang II binding to AT1 receptors. The rationale for the proposed research is that, once knowledge of the mechanisms that are responsible for the development of hypertension has been obtained, it may lead to new strategies that can be used to prevent and/or treat hypertension, thereby reducing the morbidity and mortality associated with high blood pressure.

描述（由申请人提供）：计划研究的目的是证实或反驳各种高血压模型中孤束核（NTS）中存在单独的磷脂酰肌醇3（PI 3）和促分裂原活化蛋白（MAP）激酶通路。总体目标是研究在这个大脑部位的信号机制，可能有助于持续性高血压的发展和维持。我们正在进行的研究旨在提供有关各种形式的高血压中交感神经系统的明显增强与PI 3和MAP激酶信号通路在维持高血压中的作用之间关系的初步信息。我们的初步目标是证明，PI 3和MAP激酶信号通路在NTS的（mRen-2）27转基因大鼠被激活，响应于血管紧张素II结合到AT 1受体。提出这项研究的理由是，一旦获得了导致高血压发展的机制的知识，它可能会导致可用于预防和/或治疗高血压的新策略，从而降低与高血压相关的发病率和死亡率。