Regulation of neonatal renal hemodynamics

新生儿肾脏血流动力学的调节

基本信息

批准号：
9303346
负责人：
Adebowale Adebiyi
金额：
$ 30万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9303346
关键词：
Acute Acute Renal Failure with Renal Papillary Necrosis Address Adult Agonist Area Arteries Asphyxia Attenuated Birth Blood Vessels Blood flow Calcium Channel Cations Data Electrolytes Electrophysiology (science)Event Excretory function Exhibits Family Family suidae Glomerular Filtration Rate Homeostasis Hypovolemia Image Injury Ion Channel Ischemia Kidney Kidney Diseases Kidney Failure Knowledge Laser-Doppler Flowmetry Liquid substance Maintenance Measures Membrane Microcirculation Modeling Muscle Cells Myography Neonatal Newborn Infant Organ Pathologic Pathway interactions Perfusion Perinatal Pharmacology Physiological Pilot Projects Plasma Preventive Process RNA Interference Regional Perfusion Regulation Renal Blood Flow Reperfusion Therapy Risk Role Sepsis Stretching Techniques Testing Therapeutic Time Tubular formation Ultrasonography Up-Regulation Vanilloid Vascular resistance arteriole constriction experimental study glomerular function hemodynamics hypoperfusion instrument kidney vascular structure member meter neonate new therapeutic target novel pressure protein expression public health relevance receptor renal artery renal ischemia response urinary vasoconstriction voltage

项目摘要

DESCRIPTION (provided by applicant): At birth, the newborn kidneys are functionally immature and exhibit higher vascular resistance and lower glomerular filtration rate (GFR) compared with adults. Renal immaturity put neonates at risk for kidney injury, especially when renal hemodynamics is altered by adverse perinatal events including hypovolemia, asphyxia, sepsis, and renal ischemia. Several areas of neonatal renal hemodynamics remain unexplored. In particular, mechanisms that control neonatal renal vascular tone and pathological alterations that result in hypoperfusion during acute kidney injury (AKI) are unclear. A growing body of evidence suggests that members of the transient receptor potential (TRP) family of ion channels contribute to the intrinsic regulation of vascular tone and organ blood flow. Whether TRP channels control neonatal renal vascular resistance and hemodynamics is unknown. The present application originates from preliminary findings suggesting that the vanilloid transient receptor potential (TRPV) subfamily, member 4 is expressed in neonatal preglomerular renal artery and arteriole myocytes and regulates myogenic vasoconstriction, regional kidney perfusion, and GFR. Data from our pilot studies also suggest that alterations in renal vascular TRPV4 channel expression are associated with kidney hypoperfusion in renal ischemia/reperfusion-induced neonatal AKI. The overarching hypothesis of this proposal is that activation of vascular myocyte TRPV4 channels contributes to neonatal renal blood flow autoregulation, and that alterations in renal vascular myocyte TRPV4 channel expression and activity amplify kidney hypoperfusion in neonatal AKI. To address this hypothesis, three Specific Aims will be studied using newborn pigs. We will test the hypotheses that: 1. Intravascular pressure activates myocyte TRPV4 channels, leading to membrane depolarization and vasoconstriction in neonatal renal preglomerular arteries, 2. Myocyte TRPV4 channels regulate neonatal renal microcirculation, GFR, and electrolyte homeostasis, and 3. Renal ischemia-reperfusion in neonates upregulates arterial myocyte TRPV4 channel expression and activity, leading to hypoperfusion and a reduction in GFR. This application will identify TRPV4 channels as an important modulator of glomerular functions in neonates.

描述（由申请人提供）：出生时，与成年人相比，新生儿肾脏在功能上不成熟，表现出较高的血管耐药性和较低的肾小球滤过率（GFR）。肾脏不成熟使新生儿面临肾脏损伤的风险，尤其是当不良围产期事件（包括无毒，窒息，败血症和肾脏缺血）改变肾脏血液动力学时。新生儿肾脏血流动力学的几个区域仍未探索。特别是，控制新生儿肾血管张力张力和病理改变的机制尚不清楚急性肾损伤（AKI）期间灌注不足的机制。越来越多的证据表明，离子通道的瞬时受体电位（TRP）家族的成员有助于血管张力和器官血流的内在调节。 TRP通道是否控制新生儿肾脏血管抗性和血液动力学尚不清楚。本应用起源于初步发现，表明香草素瞬态受体电位（TRPV）亚家族，成员4在新生儿前胶质细胞前肾动脉和动脉心肌细胞中表达，并调节肌源性血管收缩，区域肾脏灌注和GFR。我们的试点研究的数据还表明，肾脏血管TRPV4通道表达的改变与肾脏缺血/再灌注引起的新生儿AKI中的肾脏灌注有关。该提案的总体假设是，血管肌细胞TRPV4通道的激活有助于新生儿血液流动自动调节，并且肾血管肌细胞TRPV4通道表达和活性在新生儿AKI中的肾脏肾脏灌注不足。为了解决这一假设，将使用新生儿猪研究三个特定目标。我们将测试以下假设：1。血管内压力激活心肌TRPV4通道，从而导致新生儿肾脏前动脉的膜增压和血管收缩2。肌细胞TRPV4通道调节新生儿肾脏微循环，GRFR，GRFR，GR，和电解剂，以及3。RENERFR，3。RENERFER-3。RENERFER-3.。上调动脉肌细胞TRPV4通道表达和活性，导致灌注不足和GFR的降低。该应用程序将识别TRPV4通道是新生儿肾小球功能的重要调节剂。