FETAL HYPOXEMIA AND ENDOTHELIUM DERIVED NITRIC OXIDE
FETAL HYPOXEMIA AND ENDOTHELIUM DERIVED NITRIC OXIDE
批准号:
2697786
负责人:
LOREN P THOMPSON
金额:
$21.02万
依托单位国家:
美国
项目类别:
财政年份:
1993
资助国家:
美国
项目状态:
已结题
起止时间:
1993-05-01 至 2001-06-30
关键词:
RNase protection assay brain carotid artery cerebral artery embryo /fetus hypoxia gene expression guinea pigs heart circulation immunocytochemistry lung messenger RNA microcirculation molecular cloning nitric oxide nitric oxide synthase nucleic acid probes oxygen tension pulmonary artery solution hybridization statistics /biometry vascular endothelium vascular resistance vasoconstriction vasodilation video microscopy
中文摘要
低氧血症是导致胎儿发病率和死亡率的主要原因之一。
胎儿再分布的血管机制
低氧血症时的心输出量知之甚少。我们建议
慢性低氧血症改变内皮细胞一氧化氮基因表达
突触、诱导型一氧化氮合酶与血管反应性
对减少的氧合的适应性反应。我们的初步数据
显示长期的低氧血症增加了胎儿的心脏和减少了胎儿
前脑enos基因的表达。此外,持续4天的低氧血症抑制了
胎儿颈动脉内皮依赖性的松弛,但
7天后逆转。因此,胎儿低氧血症影响两种一氧化氮合酶基因
器官特异性表达与NO介导的松弛
孤立的胎儿动脉。一氧化氮在血管调节中的作用
将研究胎儿对慢性低氧血症的适应情况
12%O2,持续4、7或14天,以达到以下目的。目标1:测试
长期低氧血症改变eNOS基因表达的假说
胚胎豚鼠脏器和动脉组织中均有iNOS基因表达。靶向mRNA
会在胎儿的大脑、心脏和肺中被检测和量化为
以及由核糖核酸酶保护的颈动脉和肺动脉
化验。目的2:检验长期低氧血症的假设
减弱胎儿离体肺和颈动脉的扩张器反应
抑制eNOS基因表达和内皮源性NO对动脉的影响
制作。目的3:检验长期低氧血症的假设
抑制离体胎脑动脉的松弛。的影响
慢性低氧血症对激动剂刺激的松弛、氧敏感性的影响
胎儿血管内皮细胞,血流刺激的松弛将
在视频显微镜装置上对分离的大脑动脉进行测量。
目的4:验证长期低氧血症增加扩张器的假设
胎儿冠状动脉微循环的反应。因此,这项提议
将确定一氧化氮合酶基因表达和内皮衍生的作用
NO作为对胎儿缺氧应激的适应性反应。
英文摘要
Hypoxemia is one of the leading causes of fetal morbidity and mortality.
The vascular mechanisms responsible for the redistribution of fetal
cardiac output during hypoxemia are poorly understood. We propose that
chronic hypoxemia alters gene expression of endothelial nitric oxide
synapse (eNOS) and inducible NOS (iNOS) and vascular reactivity as
adaptive responses to the reduced oxygenation. Our preliminary data
show that prolonged hypoxemia increases fetal heart and decreases fetal
forebrain eNOS mRNA expression. Further, hypoxemia for 4 days inhibits
the endothelium-dependent relaxation of the fetal carotid artery but is
reversed after 7 days. Thus, fetal hypoxemia affects both NOS gene
expression in an organ specific manner and NO-mediated relaxation of
isolated fetal arteries. The role of NO in mediating the vascular
adaptations to chronic hypoxemia will be studied in fetuses exposed to
12 percent O2 for 4,7,or 14 days in the following aims. Aim 1: To test
the hypothesis that prolonged hypoxemia alters gene expression of eNOS
and iNOS mRNA in both fetal guinea pig organs and arteries. Target mRNA
will be detected and quantified in the fetal brain, heart, and lung as
well as carotid and pulmonary arteries by a ribonuclease protection
assay. Aim 2: To test the hypothesis that prolonged hypoxemia
attenuates dilator responses of isolated fetal pulmonary and carotid
arteries by inhibiting eNOS mRNA expression and endothelium-derived NO
production. Aim 3: To test the hypothesis that prolonged hypoxemia
inhibits relaxation of isolated fetal cerebral arteries. The effect of
chronic hypoxemia on agonist-stimulated relaxation, oxygen sensitivity
of the fetal vascular endothelium, and flow-stimulated relaxation will
be measured in isolated cerebral arteries on a video microscopy setup.
Aim 4: To test the hypothesis that prolonged hypoxemia increases dilator
responses of the fetal coronary microcirculation. Thus, this proposal
will identify the role of NOS gene expression and endothelium-derived
NO as adaptive responses to fetal hypoxic stress.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Impact of Prenatal Hypoxia on Mitochondrial Function of Offspring Hearts
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批准号:10218255
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项目类别:
-
资助金额:$52.92万
-
财政年份:2015
-
负责人:LOREN P THOMPSON
-
依托单位:
Impact of Prenatal Hypoxia on Mitochondrial Function of Offspring Hearts
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批准号:10412069
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项目类别:
-
资助金额:$52.92万
-
财政年份:2015
-
负责人:LOREN P THOMPSON
-
依托单位:
Impact of Prenatal Hypoxia on Mitochondrial Function of Offspring Hearts
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批准号:9925279
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项目类别:
-
资助金额:$52.92万
-
财政年份:2015
-
负责人:LOREN P THOMPSON
-
依托单位:
Impact of Prenatal Hypoxia on Mitochondrial Function of Offspring Hearts
-
批准号:9483752
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项目类别:
-
资助金额:$38.38万
-
财政年份:2015
-
负责人:LOREN P THOMPSON
-
依托单位:
Aspen Perinatal Biology Conference
-
批准号:8004491
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项目类别:
-
资助金额:$0.6万
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财政年份:2010
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负责人:LOREN P THOMPSON
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依托单位:
OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM
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批准号:2226084
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项目类别:
-
资助金额:$9.56万
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财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and endothelium derived nitric oxide
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批准号:6725382
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项目类别:
-
资助金额:$25.99万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and endothelium derived nitric oxide
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批准号:6623792
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项目类别:
-
资助金额:$25.99万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and Endothelium Derived Nitric Oxide
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批准号:7805476
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项目类别:
-
资助金额:$33.75万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM
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批准号:2226082
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项目类别:
-
资助金额:$9.78万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM
-
批准号:2226081
-
项目类别:
-
资助金额:$9.4万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and Endothelium Derived Nitric Oxide
-
批准号:7314573
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项目类别:
-
资助金额:$33.75万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and Endothelium Derived Nitric Oxide
-
批准号:7469428
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项目类别:
-
资助金额:$36.12万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and Endothelium Derived Nitric Oxide
-
批准号:7640960
-
项目类别:
-
资助金额:$33.75万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
FETAL HYPOXEMIA AND ENDOTHELIUM DERIVED NITRIC OXIDE
-
批准号:6183035
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项目类别:
-
资助金额:$22.13万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and endothelium derived nitric oxide
-
批准号:6865638
-
项目类别:
-
资助金额:$25.99万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM
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批准号:3474130
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项目类别:
-
资助金额:$10.45万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
FETAL HYPOXEMIA AND ENDOTHELIUM DERIVED NITRIC OXIDE
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批准号:6030655
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项目类别:
-
资助金额:$21.72万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
Fetal Hypoxemia and endothelium derived nitric oxide
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批准号:6470226
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项目类别:
-
资助金额:$25.99万
-
财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM
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批准号:2226083
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项目类别:
-
资助金额:$0.67万
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财政年份:1993
-
负责人:LOREN P THOMPSON
-
依托单位:
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