HORMONAL REGULATION OF BLOOD PRESSURE

血压的荷尔蒙调节

• 批准号: 8256755
• 负责人: Michal Laniado Schwartzman
• 金额: $ 228.57万
• 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/8256755
• 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; 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）：该计划项目赠款的目的继续集中于细胞色素P450（CYP）衍生的类固醇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-eicosanoid研究框架提供了范式和科学领导。该计划研究者和其他研究表明，CYP-伊卡诺尔德人与包括糖尿病，中风和高血压在内的CYP-EICOSANOLDS和心血管疾病之间的分子和功能关联，在最近的研究中强调了这一与人类健康研究的相关性。该提议建立在这个基础的基础上，并将新颖的概念和新方向带到了这一研究领域。它结合了高血压的血管和肾脏机制以及CYP衍生的eicosanoids，Eets和20-Hete之间的相互作用，以及两个不同的调节回路，两种不同的调节回路，肾素 - 血管紧张素系统（RAS）和血红素加氧酶（HO）（HO）。这个主题在三个项目中描述。项目1的重点是CYP4A衍生的20-HETE与肾素血管紧张素系统之间的相互作用，并研究了内皮ACE在20-Hete介导的血管功能障碍和高血压中的作用。项目2研究了K+摄入量和血管紧张素II在调节CYP2C44依赖性EET对钠转运（上皮Na+通道）在皮质收集管道中的抑制作用及其对高血压的影响。项目3确定了HO-1和EET之间的相互作用调节脂肪细胞功能和脂联素水平的分子机制，以防止肥胖诱导的高血压中血管功能障碍的发展。这些项目将得到三个核心的支持：核心A提供行政支持。 Core B提供了基于LC-MS/MS的类eicosanoids测量值。 Core C为动物研究提供了分子，基因型和表型支持。该计划项目结合了跨学科的方法，以探索Eets和Hetes的综合生物学，肾脏盐处理的关键调节剂，血管内皮完整性和血管张力在高血压和心血管疾病的病理生理学中。 该计划项目赠款的目的继续集中于细胞色素P450（CYP）衍生的类固醇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-eicosanoid研究框架提供了范式和科学领导。该计划研究者和其他研究表明，CYP-伊卡诺尔德人与包括糖尿病，中风和高血压在内的CYP-EICOSANOLDS和心血管疾病之间的分子和功能关联，在最近的研究中强调了这一与人类健康研究的相关性。该提议建立在这个基础的基础上，并将新颖的概念和新方向带到了这一研究领域。它结合了高血压的血管和肾脏机制以及CYP衍生的eicosanoids，Eets和20-Hete之间的相互作用，以及两个不同的调节回路，两种不同的调节回路，肾素 - 血管紧张素系统（RAS）和血红素加氧酶（HO）（HO）。这个主题在三个项目中描述。项目1的重点是CYP4A衍生的20-HETE与肾素血管紧张素系统之间的相互作用，并研究了内皮ACE在20-Hete介导的血管功能障碍和高血压中的作用。项目2研究了K+摄入量和血管紧张素II在调节CYP2C44依赖性EET对钠转运（上皮Na+通道）在皮质收集管道中的抑制作用及其对高血压的影响。项目3确定了HO-1和EET之间的相互作用调节脂肪细胞功能和脂联素水平的分子机制，以防止肥胖诱导的高血压中血管功能障碍的发展。这些项目将得到三个核心的支持：核心A提供行政支持。 Core B提供了基于LC-MS/MS的类eicosanoids测量值。 Core C为动物研究提供了分子，基因型和表型支持。该计划项目结合了跨学科的方法，以探索Eets和Hetes的综合生物学，肾脏盐处理的关键调节剂，血管内皮完整性和血管张力在高血压和心血管疾病的病理生理学中。 ULAR张力，在高血压和心血管疾病的病理生理学中。