HORMONAL REGULATION OF BLOOD PRESSURE

血压的荷尔蒙调节

• 批准号: 8447431
• 负责人: Michal Laniado Schwartzman
• 金额: $ 218.16万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447431
• 关键词: Accounting; Acids; Address; Adhesions; Adipocytes; Affect; Age; Albumins; Aldosterone; Alkane 1-monooxygenase; Alkenes; Alteplase; Anabolism; Androgens; Angiotensin II; Animal Experimentation; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Arachidonic Acids; Area; Binding; Biological; Biology; Blood Platelets; Blood Pressure; Blood Vessels; Brain; CYP2C9 gene; CYP2J2 gene; Carbon; Cardiovascular Diseases; Cardiovascular system; Cell Adhesion Molecules; Cell Proliferation; Cell physiology; Cells; Clinical; Complex; Cytochrome P450; Cytochrome P450 Family Gene; Cytochromes b5; DOCA; Development; Diabetes Mellitus; Diet; Dietary Fats; Disease; Distal; Duct (organ) structure; Eicosanoids; Eicosatetraenoic Acids; Endothelial Cells; Endothelin; Enzymes; Epithelial Cells; Epoxide hydrolase; Exhibits; Experimental Models; Family; Fatty acid glycerol esters; Flavoproteins; Foundations; Functional disorder; Gene Family; Generations; Genes; Genetic Models; Glycerophospholipids; Gonadal Steroid Hormones; Health; Heme; Homeostasis; Human; Hydrolysis; Hydroxyeicosatetraenoic Acids; Hydroxylation; Hypertension; Hypotension; Inbred SHR Rats; Inflammation; Inflammatory; Inflammatory Response; Injury; Intake; Ion Channel; Ion Transport; Kidney; Kidney Diseases; Lead; Leukocytes; Link; Liver; Measurement; Mediating; Mediator of activation protein; Mixed Function Oxygenases; Modeling; Molecular; Mono-S; Morbidity - disease rate; Mus; NADH; NADP; Nature; Nephrons; Obesity; Organ; Oxidoreductase; Oxygen; Oxygenases; Patch-Clamp Techniques; Pathway interactions; Pattern; Peripheral; Permeability; Phenylephrine; Play; Potassium; Potassium Channel; Prevalence; Production; Program Research Project Grants; Property; Prostaglandins; Prostaglandins I; Protein Isoforms; Proteins; Rattus; Reaction; Recording of previous events; Regulation; Regulatory Pathway; Relative (related person); Renal function; Renin-Angiotensin System; Reporting; Research; Research Personnel; Role; Seminal; Signal Pathway; Smooth Muscle Myocytes; Sodium; Sodium Chloride; Source; Specificity; Stereoisomer; Stimulus; Stroke; Substrate Specificity; Superoxides; System; Tissues; Tubular formation; Up-Regulation; Vascular Endothelium; Vascular Smooth Muscle; Vascular resistance; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Water; adiponectin; angiogenesis; autocrine; base; blood pressure regulation; cell growth; cytochrome P-450 CYP2C subfamily; cytokine; epithelial Na+ channel; heme oxygenase-1; hemodynamics; hormone regulation; interdisciplinary approach; kidney vascular structure; large-conductance calcium-activated potassium channels; member; mortality; novel; overexpression; oxidation; paracrine; pressure; prevent; programs; receptor; receptor coupling; renal epithelium; salt intake; salt sensitive; saluretic; stem; therapeutic development; tool; vascular bed; vasoconstriction

DESCRIPTION (provided by applicant): The objective of this Program Project Grant continues to concentrate on the role of the cytochrome P450 (CYP)-derived eicosanoids in the regulation of renal and vascular function and in the control of blood pressure. This Program provided paradigms and scientific leads for a framework of CYP-eicosanoid research in the field of hypertension. The relevance ofthis research to human health is highlighted in recent studies by Program investigators and others demonstrating the molecular and functional association between CYP-eicosanolds and cardiovascular disease including diabetes, stroke and hypertension. This proposal builds on this foundation and brings novel concepts and new directions to this area of research. It incorporates the vascular and renal mechanisms and the inflammatory component of hypertension in terms of interactions between the CYP-derived eicosanoids, EETs and 20-HETE, and two distinct regulatory circuits, the renin-angiotensin system (RAS) and the heme oxygenases (HO). This theme is depicted in three projects. Project 1 focuses on the interactions between the CYP4A-derived 20-HETE and the renin angiotensin system and investigate the role of endothelial ACE in 20-HETE-mediated vascular dysfunction and hypertension. Project 2 examines the role of K+ intake and angiotensin II in regulating the inhibitory effect of CYP2C44-dependent EETs on sodium transport (epithelial Na+ channel) in the cortical collecting duct and its impact on hypertension. Project 3 determines the molecular mechanisms by which an interplay between HO-1 and EETs modulates adipocyte function and adiponectin levels to prevent the development of vascular dysfunction in obesity-induced hypertension. These projects will be supported by three Cores: Core A provides administrative support. Core B provides LC-MS/MS-based measurements of eicosanoids. Core C provides molecular, genotypic and phenotypic support for animal research. This Program Project combines interdisciplinary approach to explore the integrative biology of EETs and HETEs, key modulators of renal salt handling, vascular endothelial integrity and vascular tone, in the pathophysiology of hypertension and cardiovascular disease. The objective of this Program Project Grant continues to concentrate on the role of the cytochrome P450 (CYP)-derived eicosanoids in the regulation of renal and vascular function and in the control of blood pressure. This Program provided paradigms and scientific leads for a framework of CYP-eicosanoid research in the field of hypertension. The relevance ofthis research to human health is highlighted in recent studies by Program investigators and others demonstrating the molecular and functional association between CYP-eicosanolds and cardiovascular disease including diabetes, stroke and hypertension. This proposal builds on this foundation and brings novel concepts and new directions to this area of research. It incorporates the vascular and renal mechanisms and the inflammatory component of hypertension in terms of interactions between the CYP-derived eicosanoids, EETs and 20-HETE, and two distinct regulatory circuits, the renin-angiotensin system (RAS) and the heme oxygenases (HO). This theme is depicted in three projects. Project 1 focuses on the interactions between the CYP4A-derived 20-HETE and the renin angiotensin system and investigate the role of endothelial ACE in 20-HETE-mediated vascular dysfunction and hypertension. Project 2 examines the role of K+ intake and angiotensin II in regulating the inhibitory effect of CYP2C44-dependent EETs on sodium transport (epithelial Na+ channel) in the cortical collecting duct and its impact on hypertension. Project 3 determines the molecular mechanisms by which an interplay between HO-1 and EETs modulates adipocyte function and adiponectin levels to prevent the development of vascular dysfunction in obesity-induced hypertension. These projects will be supported by three Cores: Core A provides administrative support. Core B provides LC-MS/MS-based measurements of eicosanoids. Core C provides molecular, genotypic and phenotypic support for animal research. This Program Project combines interdisciplinary approach to explore the integrative biology of EETs and HETEs, key modulators of renal salt handling, vascular endothelial integrity and vascular tone, in the pathophysiology of hypertension and cardiovascular disease. ular tone, in the pathophysiology of hypertension and cardiovascular disease.

描述（由申请人提供）：该计划项目拨款的目标继续集中于细胞色素 P450 (CYP) 衍生的类二十烷酸在调节肾脏和血管功能以及控制血压中的作用。该计划为高血压领域的 CYP-类二十烷酸研究框架提供了范例和科学线索。项目研究人员和其他人最近的研究强调了这项研究与人类健康的相关性，证明了 CYP-二十烷醇与心血管疾病（包括糖尿病、中风和高血压）之间的分子和功能关联。该提案建立在这一基础上，为该研究领域带来了新颖的概念和新的方向。它结合了血管和肾脏机制以及高血压的炎症成分，包括 CYP 衍生的类二十烷酸、EET 和 20-HETE 之间的相互作用，以及两个不同的调节回路，肾素血管紧张素系统 (RAS) 和血红素加氧酶 (HO) ）。这个主题在三个项目中得到描述。项目1重点关注CYP4A衍生的20-HETE与肾素血管紧张素系统之间的相互作用，并研究内皮ACE在20-HETE介导的血管功能障碍和高血压中的作用。项目 2 检查 K+ 摄入量和血管紧张素 II 在调节 CYP2C44 依赖性 EET 对皮质集合管钠转运（上皮 Na+ 通道）的抑制作用中的作用及其对高血压的影响。项目 3 确定了 HO-1 和 EET 之间相互作用调节脂肪细胞功能和脂联素水平的分子机制，以防止肥胖引起的高血压中血管功能障碍的发展。这些项目将由三个核心支持：核心 A 提供行政支持。核心 B 提供基于 LC-MS/MS 的类二十烷酸测量。 Core C 为动物研究提供分子、基因型和表型支持。该项目结合跨学科方法，探索 EET 和 HETE 的综合生物学，它们是肾盐处理、血管内皮完整性和血管张力的关键调节剂，在高血压和心血管疾病的病理生理学中。 该计划项目拨款的目标继续集中于细胞色素 P450 (CYP) 衍生的类二十烷酸在调节肾脏和血管功能以及控制血压中的作用。该计划为高血压领域的 CYP-类二十烷酸研究框架提供了范例和科学线索。项目研究人员和其他人最近的研究强调了这项研究与人类健康的相关性，证明了 CYP-二十烷醇与心血管疾病（包括糖尿病、中风和高血压）之间的分子和功能关联。该提案建立在这一基础上，为该研究领域带来了新颖的概念和新的方向。它结合了血管和肾脏机制以及高血压的炎症成分，包括 CYP 衍生的类二十烷酸、EET 和 20-HETE 之间的相互作用，以及两个不同的调节回路，肾素血管紧张素系统 (RAS) 和血红素加氧酶 (HO) ）。这个主题在三个项目中得到描述。项目1重点关注CYP4A衍生的20-HETE与肾素血管紧张素系统之间的相互作用，并研究内皮ACE在20-HETE介导的血管功能障碍和高血压中的作用。项目 2 检查 K+ 摄入量和血管紧张素 II 在调节 CYP2C44 依赖性 EET 对皮质集合管钠转运（上皮 Na+ 通道）的抑制作用中的作用及其对高血压的影响。项目 3 确定了 HO-1 和 EET 之间相互作用调节脂肪细胞功能和脂联素水平的分子机制，以防止肥胖引起的高血压中血管功能障碍的发展。这些项目将由三个核心支持：核心 A 提供行政支持。核心 B 提供基于 LC-MS/MS 的类二十烷酸测量。 Core C 为动物研究提供分子、基因型和表型支持。该项目结合跨学科方法，探索 EET 和 HETE 的综合生物学，它们是肾盐处理、血管内皮完整性和血管张力的关键调节剂，在高血压和心血管疾病的病理生理学中。 ulartone，在高血压和心血管疾病的病理生理学中。