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Regulation of Renal Microcirculation in Ang II-Induced Hypertension

血管紧张素II诱发高血压肾微循环的调节

基本信息

批准号：
7249769
负责人：
Oscar A. Carretero
金额：
$ 24.74万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7249769
关键词：
Accounting Acids Affect Aldosterone Amiloride Angiotensin-Converting Enzyme Inhibitors Arachidonic Acids Arts Autacoids Bathing Biostatistics Core Blood Blood Pressure Bradykinin Bradykinin B2 Receptor Cardiovascular system Cations Cells Chelating Agents Core Facility Cyclic AMP Cyclic GMP Cyclic GMP-Dependent Protein Kinases Data Data Analyses Development Diabetes Mellitus Diffuse Dilatation - action Dinoprostone Distal Doctor of Medicine Eicosanoids Endocrine Endothelium Epoprostenol Equilibrium Excretory function Feedback Filtration Funding Future Gene Deletion Guanylate Cyclase Heart Hypertrophy Hormones Hypertension In Vitro Ionophores Kidney Kidney Diseases Kininogenase Kinins Limb structure Logistics Macula densa Measures Mediating Mediation Mediator of activation protein Microcirculation Modeling Morphology Mus Mutant Strains Mice NG-Nitroarginine Methyl Ester Natriuresis Natriuretic Factors Nephrons Nephrosclerosis Nystatin Organ Oryctolagus cuniculus PTGS2 gene Pathological Dilatation Perfusion Physiological Play Principal Investigator Process Production Prostaglandin Antagonists Prostaglandin E Receptor Prostaglandins Prostaglandins I Protein Kinase Inhibitors Proteins Receptor Signaling Regulation Renal function Renin Reporting Research Design Research Personnel Resistance Reverse Transcriptase Polymerase Chain Reaction Role Signal Transduction Sodium Soluble Guanylate Cyclase Stimulus System Techniques Testing Therapeutic Effect Thick Thromboxanes Transgenic Mice Valinomycin Vascular resistance Vasoconstrictor Agents Vasodilation Vasodilation disorder Vasodilator Agents Water Work absorption arteriole autocrine basolateral membrane channel blockers epithelial Na+ channel glomerulosclerosis in vivo inhibitor/antagonist kidney vascular structure nephrin novel paracrine pressure programs protein kinase inhibitor receptor response sensor tempol vasoconstriction

项目摘要

In Ang ll-induced hypertension, the pressure natriuresis set point is shifted to a higher pressure, probably due to an increase in renal vascular resistance and Na+ reabsorption. The afferent (Af-Art) and efferent arterioles (Ef-Art) account for most renal vascular resistance; they control GFR and peritubular pressure, and thus renal function. Af-Art resistance is regulated by a balance between factors favoring vasoconstriction and those favoring vasodilatation. Our preliminary data indicate that increased Na+ delivery to the connecting tubule (CNT) causes Af-Art dilatation. This effect will here be called connecting tubule glomerular feedback (CTGF) and is a physiological factor favoring dilatation. To study the mechanism of CTGF while avoiding the influence of systemic factors, we propose to use a technique developed by us that consists of in vitro perfusion of a microdissected Af-Art and adherent CNT. The CNT not only plays an important role in Na+ absorption and K+ excretion but also synthesizes kallikrein, renin, NO and eicosanoids; however, the role of these factors in CTGF is unknown. We propose to test the general hypothesis that C7GF promotes dilatation of the Af-Art and thus antagonizes vasoconstrictor stimuli such as Ang II and TGF. CTGF is mediated by arachidonic acid metabolites. During Ang ll-induced hypertension, CTGF is enhanced due to the combined effects of Ang II, O2'andaldosterone on Na* transport; however, in theAf-Art this stimulation is bluntedby endothelium-derived constricting factors and by increased NO in the CNT. This hypothesis will be tested in the following

在血管紧张性高血压中，压力钠尿设定点向更高的压力移动，这可能是由于增加肾血管阻力和Na+重吸收。传入(Af-Art)和传出小动脉 (EF-ART)解释了大多数肾血管阻力；它们控制GFR和管周压力，从而控制肾脏功能。房颤-ART抵抗是由有利于血管收缩的因素和那些有利于血管扩张的。我们的初步数据显示，钠离子向连接小管的输送增加 (CNT)导致Af-Art扩张。这种效应在这里被称为连接小管肾小球反馈(CTGF)。是一种有利于扩张的生理因素。在避免影响的同时研究CTGF的作用机理我们建议使用我们开发的一种技术，该技术包括体外灌流一种显微解剖Af-Art和贴壁CNT。碳纳米管不仅在Na~+吸收和K~+吸收中起重要作用排泄还合成激肽释放酶、肾素、一氧化氮和二十烷类化合物；然而，这些因素在 CTGF尚不清楚。我们建议检验C7GF促进房颤-ART扩张的普遍假设从而拮抗血管收缩刺激，如血管紧张素II和转化生长因子。CTGF通过以下方式进行调节花生四烯酸代谢物。在AngⅡ诱导性高血压期间，CTGF由于 Ang II、O2‘和醛固酮联合作用对Na~*转运的影响被内皮衍生的收缩因子和CNT中增加的NO所钝化。这一假设将在以下方面进行测试