Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage
Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage
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DOI：
10.1161/01.str.0000065829.45234.69
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发表时间：
2003-05-01
期刊：
影响因子：
8.3
通讯作者：
Roman, RJ
中科院分区：
文献类型：
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作者：
Cambj-Sapunar, L;Yu, M;Roman, RJ
背景与目的：本研究探讨了5-羟色胺（1B） （5-HT1B）受体与20-羟基戊二酸（20-HETE）在大鼠蛛网膜下腔出血（SAH）后区域脑血流量（rCBF）急性下降中的相互作用。方法：采用载体、5-HT1B受体拮抗剂（半马酸异莫烷）或20-HETE合成抑制剂（HET0016）预处理大鼠，观察腹腔注射0.3 mL动脉血、人工脑脊液和5-HT对rCBF及脑脊液中20-HETE和5-HT水平的影响。我们还研究了HET0016和异山莫烷对大脑中动脉血管收缩反应和[Ca2+](i)对5-HT的变化的影响。结果：脑脊液中20- hete和5-HT水平分别从172+/-10和6+/-4升高至629+/-44 ng/mL和1163+/-200 nmol/mL。SAH后10分钟rCBF下降30%，并在接下来的2小时内保持在这一水平。阻断5-HT1B受体可阻止SAH后rCBF的持续下降。脑内注射5-HT模拟SAH，脑脊液中20-HETE水平升高至475+/-94 ng/mL， rCBF减少30%。用HET0016阻断20-HETE的合成可阻止5-HT产生的rCBF下降。Isamoltane和HET0016将分离MCA对5-HT的血管收缩反应降低了60%，并降低了从这些动脉分离的血管平滑肌细胞中5-HT产生的[Ca2+](i)的升高。结论-这些结果表明，SAH后5-HT的释放激活了5-HT1B受体和20-HETE的合成，20-HETE通过增强脑血管对5-HT的收缩反应来促进rCBF的急性下降。
Background and Purpose-This study examined the interaction between 5-hydroxytryptamine(1B) (5-HT1B)receptors and 20-hydroxyeiscosatetraenoic acid (20-HETE) in contributing to the acute fall in regional cerebral blood flow (rCBF) after subarachnoid hemorrhage (SAH) in rats.Methods-The effects of intracisternal injection of 0.3 mL of arterial blood, artificial cerebrospinal fluid, and 5-HT on rCBF and the levels of 20-HETE and 5-HT in cerebrospinal fluid were measured in rats pretreated with vehicle, a 5-HT1B receptor antagonist (isamoltane hemifumarate), or an inhibitor of the synthesis of 20-HETE (HET0016). The effects of HET0016 and isamoltane on the vasoconstrictor response and changes in [Ca2+](i) to 5-HT were also studied in middle cerebral arteries and vascular smooth muscle cells isolated from these vessels.Results-20-HETE and 5-HT levels in cerebrospinal fluid rose from 172+/-10 to 629+/-44 ng/mL and from 6+/-4 to 1163+/-200 nmol/mL, respectively, after SAH. rCBF fell by 30% 10 minutes after SAH, and it remained at this level for the next 2 hours. Blockade of 5-HT1B receptors prevented the sustained fall in rCBF seen after SAH. Intracisternal injection of 5-HT mimicked SAH by increasing 20-HETE levels in cerebrospinal fluid to 475+/-94 ng/mL and reducing rCBF by 30%. Blockade of the synthesis of 20-HETE with HET0016 prevented the fall in rCBF produced by 5-HT. Isamoltane and HET0016 reduced the vasoconstrictor response of isolated MCA to 5-HT by >60% and diminished the rise in [Ca2+](i) produced by 5-HT in vascular smooth muscle cells isolated from these arteries.Conclusions-These results suggest that the release of 5-HT after SAH activates 5-HT1B receptors and the synthesis of 20-HETE and that 20-HETE contributes to the acute fall in rCBF by potentiating the vasoconstrictor response of cerebral vessels to 5-HT.