Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage
Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage
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DOI：
10.1152/ajpheart.00857.2007
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Edvinsson, Lars
中科院分区：
文献类型：
--
作者：
Ansar, Saema;Vikman, Petter;Edvinsson, Lars
我们假设脑缺血导致血管平滑肌细胞内皮素(ET)、5-羟色胺(5-HT)和血管紧张素II(Ang II)受体表达增强。我们的目的是将蛛网膜下腔出血(SAH)后脑血管受体上调及其潜在的分子机制与局部和整体脑血流量(CBF)减少联系起来。向大鼠交叉前池注入250亩血诱导SAH。SAH后0h、1h、3h、6h、12h、24h和48h取脑动脉进行功能和分子生物学研究。用肌电图仪观察ET-1，5-氨基-色胺(5-CT)和血管紧张素Ⅱ(Ang II)的收缩反应。用实时定量聚合酶链式反应和免疫组织化学方法分别检测受体基因和蛋白的表达水平。此外，还用放射自显影方法测量了区域和全球的CBF。结果，蛛网膜下腔出血导致ET-1和5-CT收缩增强。血管紧张素Ⅱ[通过血管紧张素Ⅱ1型(AT(1))受体]引起的收缩反应增加[在血管紧张素Ⅱ2型(AT(2))受体拮抗剂PD-123319存在下]。同时，ETB、5-HT1B和AT1受体的mRNA和蛋白水平也随着时间的推移而升高。SAH后，区域性和全局性脑血流量随时间呈递减趋势。综上所述，本研究首次证实SAH可诱导ETB、5-HT1B和AT(1)受体在功能、mRNA和蛋白水平以时间依赖的方式上调。这些变化与CBF的连续下降同步发生。因此，受体表达的变化与脑血流减少之间存在时间相关性，提示存在联系。
We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 mu 1 blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 (AT(1)) receptors] induced increased contractile responses [in the presence of the ANG II type 2 (AT(2)) receptor antagonist PD-123319]. In parallel the ETB, 5-HT1B, and AT1 receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of ETB, 5-HT1B, and AT(1) receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage.