Cerebrovascular effects of endothelin-1 investigated using high-resolution magnetic resonance imaging in healthy volunteers
Cerebrovascular effects of endothelin-1 investigated using high-resolution magnetic resonance imaging in healthy volunteers
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DOI：
10.1177/0271678x19874295
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发表时间：
2019-09-09
影响因子：
6.3
通讯作者：
Ashina, Messoud
中科院分区：
文献类型：
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作者：
Hougaard, Anders;Younis, Samaira;Ashina, Messoud
内皮素-1 (ET-1) 是一种从血管内皮释放的高效血管收缩肽。 ET-1 在脑血管疾病中发挥着重要作用，并可能通过血管收缩和脑血流量 (CBF) 减少而恶化急性缺血性中风和动脉瘤性蛛网膜下腔出血的结果。增加中风风险的疾病，包括高血压、糖尿病和急性心肌梗死，与血浆 ET-1 水平升高有关。此前尚未研究过全身 ET-1 输注对人脑血管的体内影响。在双向交叉、随机、双盲设计中，我们采用先进的 3 特斯拉 MRI 方法，研究高剂量静脉注射 ET-1 对 14 名健康志愿者的颅内和外动脉周长、整体和局部 CBF 以及脑氧代谢率 (CMRO2) 的影响。输注 ET-1 后，我们观察到平均动脉血压增加 14%，大脑中动脉 (MCA) 周长减少 5%，但对脑外动脉没有影响，对 CBF 或 CMRO2 没有影响。总的来说，研究结果表明 MCA 收缩继发于血压升高，而不是由于 ET-1 的直接血管收缩作用。我们认为，与蛛网膜下腔中的 ET-1 不同，血管内 ET-1 不会对人体产生直接的脑血管作用。
Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide released from vascular endothelium. ET-1 plays a major role in cerebrovascular disorders and likely worsens the outcome of acute ischaemic stroke and aneurismal subarachnoid haemorrhage through vasoconstriction and cerebral blood flow (CBF) reduction. Disorders that increase the risk of stroke, including hypertension, diabetes mellitus, and acute myocardial infarction, are associated with increased plasma levels of ET-1. The in vivo human cerebrovascular effects of systemic ET-1 infusion have not previously been investigated. In a two-way crossover, randomized, double-blind design, we used advanced 3 tesla MRI methods to investigate the effects of high-dose intravenous ET-1 on intra- and extracranial artery circumferences, global and regional CBF, and cerebral metabolic rate of oxygen (CMRO2) in 14 healthy volunteers. Following ET-1 infusion, we observed a 14% increase of mean arterial blood pressure, a 5% decrease of middle cerebral artery (MCA) circumference, but no effects on extracerebral arteries and no effects on CBF or CMRO2. Collectively, the findings indicate MCA constriction secondarily to blood pressure increase and not due to a direct vasoconstrictor effect of ET-1. We suggest that, as opposed to ET-1 in the subarachnoid space, intravascular ET-1 does not exert direct cerebrovascular effects in humans.