HORMONAL REGULATION OF BLOOD PRESSURE

血压的荷尔蒙调节

• 批准号: 8827392
• 负责人: Michal Laniado Schwartzman
• 金额: $ 220.11万
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8827392
• 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 Diseases; Vascular Endothelium; Vascular Smooth Muscle; Vascular resistance; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Water; adiponectin; angiogenesis; autocrine; base; blood pressure reduction; blood pressure regulation; cell growth; cytochrome P-450 CYP2C subfamily; cytokine; endothelial dysfunction; 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 hypertension; 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）：本计划项目资助的目标继续集中在细胞色素P450（CYP）衍生的类花生酸在调节肾和血管功能以及控制血压中的作用。该项目为高血压领域CYP-类花生酸的研究框架提供了范例和科学线索。这项研究与人类健康的相关性在最近的研究中得到了强调，这些研究表明CYP-二十烷酸与心血管疾病（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，并为这一研究领域带来了新的概念和新的方向。它结合了血管和肾脏机制以及高血压的炎症组分，涉及CYP衍生的类二十烷酸、雌二醇和20-HETE之间的相互作用，以及两种不同的调节回路，即肾素-血管紧张素系统（RAS）和血红素加氧酶（HO）。这一主题体现在三个项目中。项目1主要研究CYP 4A衍生的20-HETE与肾素-血管紧张素系统的相互作用，并探讨内皮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+摄入和血管紧张素II在调节CYP 2C 44依赖性EkB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和雌二醇之间的相互作用调节脂肪细胞功能和脂联素水平以防止肥胖诱导的高血压中血管功能障碍的发展的分子机制。这些项目将由三个核心支助：核心A提供行政支助。核心B提供类二十烷酸的基于LC-MS/MS的测量。核心C为动物研究提供分子、基因型和表型支持。该计划项目结合了跨学科的方法来探索Ehrs和HETE的整合生物学，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。 该项目资助的目标继续集中在细胞色素P450（CYP）衍生的类花生酸在调节肾和血管功能以及控制血压中的作用。该项目为高血压领域CYP-类花生酸的研究框架提供了范例和科学线索。这项研究与人类健康的相关性在最近的研究中得到了强调，这些研究表明CYP-二十烷酸与心血管疾病（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，并为这一研究领域带来了新的概念和新的方向。它结合了血管和肾脏机制以及高血压的炎症组分，涉及CYP衍生的类二十烷酸、雌二醇和20-HETE之间的相互作用，以及两种不同的调节回路，即肾素-血管紧张素系统（RAS）和血红素加氧酶（HO）。这一主题体现在三个项目中。项目1主要研究CYP 4A衍生的20-HETE与肾素-血管紧张素系统的相互作用，并探讨内皮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+摄入和血管紧张素II在调节CYP 2C 44依赖性EkB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和雌二醇之间的相互作用调节脂肪细胞功能和脂联素水平以防止肥胖诱导的高血压中血管功能障碍的发展的分子机制。这些项目将由三个核心支助：核心A提供行政支助。核心B提供类二十烷酸的基于LC-MS/MS的测量。核心C为动物研究提供分子、基因型和表型支持。该计划项目结合了跨学科的方法来探索Ehrs和HETE的整合生物学，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。在高血压和心血管疾病的病理生理学中。

项目成果

WNK4 inhibits Ca(2+)-activated big-conductance potassium channels (BK) via mitogen-activated protein kinase-dependent pathway.

• DOI: 10.1016/j.bbamcr.2013.05.004
• 发表时间: 2013-10
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
• 影响因子: 5.1
• 作者: Yue, Peng;Zhang, Chengbiao;Lin, Dao-Hong;Sun, Peng;Wang, Wen-Hui
• 通讯作者: Wang, Wen-Hui

The emerging role of heme oxygenase and its metabolites in the regulation of cardiovascular function.

血红素加氧酶及其代谢物在心血管功能调节中的新作用。

• DOI: 10.1155/2012/593530
• 发表时间: 2012
• 期刊: International journal of hypertension
• 影响因子: 1.9
• 作者: Stec DE;Ishikawa K;Sacerdoti D;Abraham NG
• 通讯作者: Abraham NG

Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity.

• DOI: 10.1155/2016/8197325
• 发表时间: 2016
• 期刊: Stem cells international
• 影响因子: 4.3
• 作者: Sodhi K;Hilgefort J;Banks G;Gilliam C;Stevens S;Ansinelli HA;Getty M;Abraham NG;Shapiro JI;Khitan Z
• 通讯作者: Khitan Z

Improved myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signaling.

• DOI: 10.1002/jcb.22486
• 发表时间: 2010-04-01
• 期刊: JOURNAL OF CELLULAR BIOCHEMISTRY
• 影响因子: 4
• 作者: Kusmic, Claudia;L'Abbate, Antonio;Sambuceti, Gianmario;Drummond, George;Barsanti, Cristina;Matteucci, Marco;Cao, Jian;Piccolomini, Francesco;Cheng, Jennifer;Abraham, Nader G.
• 通讯作者: Abraham, Nader G.

NFAT5 is protective against ischemic acute kidney injury.

• DOI: 10.1161/hypertensionaha.113.02476
• 发表时间: 2014-03
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Hao S;Bellner L;Zhao H;Ratliff BB;Darzynkiewicz Z;Vio CP;Ferreri NR
• 通讯作者: Ferreri NR