INTERACTION OF NO AND ET-1 IN PULMONARY HYPERTENSION
INTERACTION OF NO AND ET-1 IN PULMONARY HYPERTENSION
批准号:
6439945
负责人:
IVAN F MCMURTY
金额:
$12.36万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-04-01 至 2002-03-31
关键词:
calcium flux endothelin gene expression genetic disorder genetic strain hormone receptor in situ hybridization laboratory rat nitric oxide nitric oxide synthase northern blottings pathologic process perfusion pulmonary hypertension respiratory hypoxia respiratory pharmacology tissue /cell culture vascular endothelium vascular resistance vascular smooth muscle vasoconstriction vasoconstrictors vasomotion western blottings
中文摘要
人类和动物研究表明,减少一氧化氮(NO)
血管舒张和内皮素血管收缩增加是关键成分
肺动脉高压(PH)的发病机制。但有
关于联合国作用的不确定性和争议的重要领域
这两个调解人,更好地了解规则,
NO和ET-1在PH实验模型中的相互作用将有助于
为各种血管疾病开发更有效的治疗方法
疾病我们有初步的结果,与高血压相比,
慢性缺氧性白化病大鼠的肺表达增加的水平,
内皮型一氧化氮合酶mRNA和蛋白质,但很少或没有增加ET-1,
常氧小鹿冠大鼠自发性高血压肺表达
eNOS水平降低,ET-1 mRNA和肽水平升高。这些
和其他研究结果表明,有显着差异,在
eNOS和ET-1基因表达及NO-1和ET-1的调控
血管反应性在这两种动物模型的PH。因此,我们的整体
一种假说认为,
不同形式的NO血管舒张和ET-1血管收缩的调节
为了验证这个想法,生理学,药理学和分子生物学
生物技术将用于完整大鼠和离体大鼠肺,
比较肺和肺血管的基因表达,生产,
缺氧与自发(驼色)NO和ET-1的血管反应性
博士具体目的是检验以下假设:1)当缺氧PH
与eNOS mRNA和蛋白表达增加有关,
ET-1轻度升高,自发PH值下降
高血压血管紧张度
是由于缺氧肺中NO合成减少和高水平的
ET-1在驼鹿肺中的表达,并由ETA和ETB差异介导
3)缺氧时eNOS表达上调,
高血压肺是由于缺氧的非血流动力学效应,
在自发性高血压肺中ET-1的增加扩张,
对血流动力学信号的反应。
英文摘要
Human and animal studies suggest that decreased nitric oxide (NO)
vasodilation and increased endothelin vasoconstriction are key components
of the pathogenesis of pulmonary hypertension (PH). However, there are
important areas of uncertainty and controversy regarding the roles of
these two mediators, and better understanding of the regulation and
interaction of NO and ET-1 in experimental models of PH would be useful in
the development of more effective therapies for the diverse vascular
disease. We have preliminary results that in contrast to the hypertensive
lungs of chronically-hypoxic albino rats which express increased levels of
eNOS MRNA and protein but little or no increase in ET-1, the
spontaneously-hypertensive lungs of normoxic fawn-hooded rats express
decreased levels of eNOS but high levels of ET-1 mRNA and peptide. These
and other findings indicate that there are significant differences in the
regulation of eNOS and ET-1 gene expression and NO1 and ET-1
vasoreactivity in these two animal models of PH. Thus, our overall
hypothesis is that there are important differences in mechanisms of
regulation of NO vasodilation and ET-1 vasoconstriction in different forms
of PH. To test this idea, physiologic, pharmacologic, and molecular
biologic techniques will be used in intact rats and isolated rat lungs to
compare lung and pulmonary vascular gene expression, production, and
vasoreactivity of NO and ET-1 in hypoxic versus spontaneous (fawn-hooded)
PH. The specific aims are to test the hypothesis that: 1) while hypoxic PH
is associated with increased expression of eNOS mRNA and protein but
little increase in ET-1, spontaneous PH is accompanied by decreased
expression of eNOS but high levels of ET-1, 2) hypertensive vascular tone
is due to decreased No synthesis in hypoxic lungs and to high levels of
ET-1 in fawn-hooded lungs and is differentially mediated by ETA and ETB
receptors in the two models, 3) upregulation of eNOS in hypoxic
hypertensive lungs is due to non-hemodynamic effects of hypoxia, and the
increased expansion of ET-1 in spontaneously-hypertensive lungs is in
response to hemodynamic signals.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Rho/Rho kinase in hypoxic pulmonary hypertension
-
批准号:7371909
-
项目类别:
-
资助金额:$42.17万
-
财政年份:2007
-
负责人:IVAN F MCMURTY
-
依托单位:
Rho/Rho kinase in hypoxic pulmonary hypertension
-
批准号:6728395
-
项目类别:
-
资助金额:$22.08万
-
财政年份:2003
-
负责人:IVAN F MCMURTY
-
依托单位:
INTERACTION OF NO AND ET-1 IN PULMONARY HYPERTENSION
-
批准号:6630915
-
项目类别:
-
资助金额:$12.36万
-
财政年份:2002
-
负责人:IVAN F MCMURTY
-
依托单位:
INTERACTION OF NO AND ET-1 IN PULMONARY HYPERTENSION
-
批准号:6324720
-
项目类别:
-
资助金额:$17.35万
-
财政年份:2000
-
负责人:IVAN F MCMURTY
-
依托单位:
INTERACTION OF NO AND ET-1 IN PULMONARY HYPERTENSION
-
批准号:6109376
-
项目类别:
-
资助金额:$17.35万
-
财政年份:1999
-
负责人:IVAN F MCMURTY
-
依托单位:
INTERACTION OF NO AND ET-1 IN PULMONARY HYPERTENSION
-
批准号:6272508
-
项目类别:
-
资助金额:$17.19万
-
财政年份:1998
-
负责人:IVAN F MCMURTY
-
依托单位:
EDRF MODULATION OF PULMONARY HYPERTENSION
-
批准号:6241513
-
项目类别:
-
资助金额:$21.49万
-
财政年份:1997
-
负责人:IVAN F MCMURTY
-
依托单位:
Rho/Rho kinase in hypoxic pulmonary hypertension
-
批准号:7049536
-
项目类别:
-
资助金额:$23.87万
-
财政年份:--
-
负责人:IVAN F MCMURTY
-
依托单位:
Rho/Rho kinase in hypoxic pulmonary hypertension
-
批准号:7198038
-
项目类别:
-
资助金额:$24.59万
-
财政年份:--
-
负责人:IVAN F MCMURTY
-
依托单位:
国内基金
海外基金
内皮素Endothelin-1诱导皮层扩散性抑制的在体光学成像研究
-
批准号:30500115
-
项目类别:青年科学基金项目
-
资助金额:29.0万元
-
批准年份:2005
-
负责人:李鹏程
-
依托单位: