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首页> 外文期刊>PLoS One >Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries
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Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

机译：蛛网膜下腔出血和血管痉挛患者的脑脊液增强大鼠脑动脉内皮素的收缩。

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Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. Conclusions Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients with SAH.
机译：引言先前的研究表明，蛛网膜下腔出血（SAH）患者的脑脊液可导致孤立动脉的明显血管收缩。我们假设只有SAH血管痉挛患者的脑脊液会在大鼠脑动脉中产生对内皮素1的增强收缩反应，涉及内皮素ETA和ETB受体。方法将完整的大鼠基底动脉与1）SAH血管痉挛患者，2）SAH无血管痉挛患者和3）对照患者的脑脊液孵育24小时。将有和没有内皮的动脉段安装在肌电描记器中，并在不存在和存在选择性和联合ETA和ETB受体拮抗剂的情况下，构建内皮素1的浓度-反应曲线。测量培养基中的内皮素浓度和受体表达。结果与其他组相比，在血管痉挛患者的暴露于脑脊液的动脉中观察到以下情况：1）在较低的内皮素浓度下收缩较大（p <0.05）; 2）在没有内皮的动脉中没有内皮素的增加收缩; 3）培养基中内皮素分泌水平较高（p <0.05）; 4）有ETA受体表达，ETB受体新表达明显。 5）在低浓度范围内ETB阻断后和高浓度范围内ETA阻断后对内皮素增强反应的降低; 6）联合ETA和ETB阻断后，观察到内皮素收缩完全抑制。结论我们的实验结果表明，在暴露于血管痉挛患者的脑脊液中的完整大鼠基底动脉中，内皮素收缩以内皮依赖性方式增强，并被ETA和ETB受体联合拮抗。因此，我们建议两种受体的联合阻断可能在抵抗SAH患者的血管痉挛中发挥作用。

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