Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Glostrup, Denmark.
Department of Clinical Experimental Research, Rigshospitalet Glostrup, Glostrup, Denmark.
J Cereb Blood Flow Metab. 2020 Aug;40(8):1685-1694. doi: 10.1177/0271678X19874295. Epub 2019 Sep 9.
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 (CMRO) 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 CMRO. 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.
内皮素-1（ET-1）是一种从血管内皮释放的强效血管收缩肽。ET-1 在脑血管疾病中起主要作用，并可能通过血管收缩和脑血流（CBF）减少使急性缺血性中风和动脉瘤性蛛网膜下腔出血的预后恶化。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。全身 ET-1 输注对人类脑血管的体内影响以前尚未被研究过。在一项双向交叉、随机、双盲设计中，我们使用先进的 3 特斯拉 MRI 方法，在 14 名健康志愿者中研究了高剂量静脉内 ET-1 对颅内和颅外动脉周长、全脑和区域性 CBF 以及脑氧代谢率（CMRO）的影响。在 ET-1 输注后，我们观察到平均动脉血压升高 14%，大脑中动脉（MCA）周长减少 5%，但对颅外动脉没有影响，对 CBF 或 CMRO 也没有影响。总的来说，这些发现表明 MCA 收缩是血压升高的继发性反应，而不是 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 不会在人类中产生直接的脑血管作用。
