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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：
9520312
负责人：
Adebowale Adebiyi
金额：
$ 37.6万
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 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9520312
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 Messenger RNA Microcirculation Modeling Muscle Cells Myography Neonatal Newborn Infant Organ Pathologic Pathway interactions Perfusion Perinatal Pharmacology Physiological Pilot Projects Plasma Preventive Process Proteins 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，新生儿肾脏功能不成熟，与成人相比，血管阻力较高，肾小球滤过率（GFR）较低。肾不成熟使新生儿处于肾损伤的风险中，特别是当肾血流动力学被不良围产期事件改变时，包括低血容量、窒息、败血症和肾缺血。新生儿肾脏血流动力学的几个领域仍然没有探索。特别是，机制，控制新生儿肾血管紧张度和病理改变，导致低灌注在急性肾损伤（阿基）还不清楚。越来越多的证据表明，瞬时受体电位（TRP）离子通道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血管阻力和血流动力学尚不清楚。本申请源自初步发现，表明香草素瞬时受体电位（TRPV）亚家族成员4在新生儿肾小球前肾动脉和小动脉肌细胞中表达，并调节肌源性血管收缩、局部肾灌注和GFR。来自我们的初步研究的数据还表明，肾血管TRPV 4通道表达的改变与肾缺血/再灌注诱导的新生儿阿基中的肾灌注不足相关。该提议的首要假设是，血管肌细胞TRPV 4通道的激活有助于新生儿肾血流自动调节，并且肾血管肌细胞TRPV 4通道表达和活性的改变放大了新生儿阿基中的肾灌注不足。为了解决这一假设，将使用新生猪研究三种特定目的。我们将测试的假设是：1。血管内压力激活肌细胞TRPV 4通道，导致新生儿肾小球前动脉膜去极化和血管收缩。肌细胞TRPV 4通道调节新生儿肾微循环、GFR和电解质稳态，以及3.新生儿肾缺血再灌注可上调动脉肌细胞TRPV 4通道表达和活性，导致灌注不足和GFR降低。本申请将鉴定TRPV 4通道作为新生儿肾小球功能的重要调节剂。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species.

DOI：
10.3390/ijms22147589
发表时间：
2021-07-15
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Matthews AT;Soni H;Robinson-Freeman KE;John TA;Buddington RK;Adebiyi A
通讯作者：
Adebiyi A

Activation of the cannabinoid receptor 2 increases renal perfusion.

大麻素受体 2 的激活会增加肾灌注。

DOI：
10.1152/physiolgenomics.00001.2019
发表时间：
2019
期刊：
Physiological genomics
影响因子：
4.6
作者：
Pressly,JD;Soni,H;Jiang,S;Wei,J;Liu,R;Moore,BM;Adebiyi,A;Park,F
通讯作者：
Park,F

Adenosine A1 receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels.

腺苷 A1 受体操纵的钙进入肾传入小动脉依赖于出生后 TRPC3 通道的成熟。

DOI：
10.1152/ajprenal.00335.2017
发表时间：
2017
期刊：
American journal of physiology. Renal physiology
影响因子：
0
作者：
Soni,Hitesh;Peixoto-Neves,Dieniffer;Buddington,RandalK;Adebiyi,Adebowale
通讯作者：
Adebiyi,Adebowale

KV7.1 channel blockade inhibits neonatal renal autoregulation triggered by a step decrease in arterial pressure.

KV7.1 通道阻断可抑制由动脉压逐步降低引发的新生儿肾脏自动调节。

DOI：
10.1152/ajprenal.00568.2020
发表时间：
2022
期刊：
American journal of physiology. Renal physiology
影响因子：
0
作者：
Peixoto-Neves,Dieniffer;Kanthakumar,Praghalathan;Afolabi,JeremiahM;Soni,Hitesh;Buddington,RandalK;Adebiyi,Adebowale
通讯作者：
Adebiyi,Adebowale

TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways.