CEREBRAL ISCHEMIA--ENDOTHELIN-1 AND NITRIC OXIDE
脑缺血——内皮素-1 和一氧化氮
基本信息
- 批准号:2579677
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
We have explored the possibility of imbalance between the production of
endothelin-1 (ET-1) and nitric oxide (NO) which may exacerbate brain
injury. ET-1 a known potent vasoconstrictor peptide and NO, an
endothelial relaxing factor, are produced among other vasoactive
mediators in the vascular endothelium and in other cells in the brain.
It has been suggested that an imbalance between the production of ET-1
and NO in the endothelium may play a role in cerebrovascular disorders.
In particular, the observed increased ET-1 levels in plasma and/or
cerebrospinal fluid (CSF) of patients with stroke, hypertension and
vasospasm implicate ET-1 in the pathogenesis of cerebrovascular disease
process. The aim of this study was to establish whether cerebral
ischemia leads to CSF elevation of ET-1 which could be additionally
altered by inhibition of NO synthase (NOS). Bilateral carotid artery
occlusion (15 min) alone or with release (5-120 min) in gerbils served
as a model for cerebral ischemia. The treatment consisted of either
nitro-L-arginine (NLA) or D-nitro-L-arginine methyl ester (D-NAME) 40
mg/kg b.w.) in Ringer's solution (0.5ml) or the solvent alone given
intraperitoneally 4 hr prior to the induction of ischemia. Similarly
treated sham-operated animals were used as controls. Systemic blood
pressure (SBP), cerebral blood flow (CBF), temporal and rectal
temperature were continuously monitored in anesthetized (halothane 1.5%
and NO2/O2 1%) and spontaneously ventilated gerbils. CSF was obtained
from the cisterna magna at the end of each experimental period. The level
of ET-1 in CSF was measured by radioimmunoassay. Temperature was not
significantly affected by either treatment. SBP was only elevated in NLA-
treated animals during pre- and postischemia (NLA 77.67 plus minus 1.88
and 85.33 plus minus1.75 mm Hg, respectively; others 66.67 plus minus
3.45 and 72.5 plus minus 2.17 mm Hg, respectively), although ischemia
induced a similar rise in SBP in all groups of gerbils. CBF was reduced
(0.5% of control) during ischemia in all groups. NLA treatment but not
D-NAME prevented the initial complete recovery of CBF during reperfusion
(7.5 min). In the CSF, the ET-1 level was raised 2-3 fold over controls
in early reperfusion after 15 min of ischemia. The NLA-treated animals
already showed the increased content of ET-1 in the CSF after ischemia
alone with reperfusion. This is the first demonstration of changes in ET-
1 content of CSF in ischemia/reperfusion. NOS inhibition produces an
early and persistent rise in ET-1 levels of CSF in addition to SBP
elevation and incomplete recovery of CBF during ischemia/reperfusion.
我们已经探讨了生产之间不平衡的可能性,
内皮素-1(ET-1)和一氧化氮(NO)可能会加重脑
损伤ET-1是一种已知的有效的血管收缩肽,NO是一种血管紧张素,
内皮舒张因子是在其他血管活性物质中产生的,
在血管内皮细胞和大脑中的其他细胞中的介质。
有人认为,ET-1的产生之间的不平衡
内皮细胞NO可能在脑血管疾病中起一定作用。
特别地,所观察到的血浆和/或组织中ET-1水平的增加,
脑卒中、高血压和高血压患者的脑脊液(CSF)
血管痉挛提示ET-1参与脑血管病的发病机制
过程 这项研究的目的是确定大脑是否
缺血导致CSF中ET-1升高,这可能是额外的
通过抑制NO合酶(NOS)改变。双侧颈动脉
在沙鼠中单独封闭(15分钟)或释放(5-120分钟)
作为脑缺血的模型。 治疗包括
硝基-L-精氨酸(NLA)或D-硝基-L-精氨酸甲酯(D-NAME)40
(毫克/千克体重)在林格氏溶液(0.5ml)中或在给定的单独溶剂中
在诱导缺血前4小时腹膜内注射。 类似地
将处理的假手术动物用作对照。 全身血液
血压(SBP),脑血流量(CBF),颞和直肠
在麻醉(氟烷1.5%)中连续监测温度
和NO2/O2 1%)和自发通气沙鼠。 获得CSF
在每个实验期结束时从小脑延髓池中取出。水平
放免法测定脑脊液中ET-1的含量。温度不
受到任何一种治疗的影响。SBP仅在NLA中升高-
在缺血前和缺血后治疗的动物(NLA 77.67 ± 1.88
85.33 ± 1.75 mm Hg,其余为66.67 ± 1.75 mm Hg
3.45和72.5 ± 2.17 mm Hg),尽管缺血
在所有沙鼠组中诱导了类似的SBP升高。CBF降低
(0.5%的对照)。NLA治疗,但不
D-NAME阻止再灌注期间CBF的最初完全恢复
(7.5 min)。CSF中ET-1水平升高2-3倍
缺血15 min后再灌注早期。NLA给药动物
已显示缺血后CSF中ET-1含量增加
单独进行再灌注。这是第一次证明ET的变化-
1.脑缺血再灌注时CSF含量。 一氧化氮合酶抑制产生
除了SBP外,CSF中ET-1水平早期和持续升高
缺血/再灌注期间CBF升高和不完全恢复。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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