Department of Neurosurgery, University of Munich Medical Center–Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Stroke. 2012 Jan;43(1):227-32. doi: 10.1161/STROKEAHA.111.626168. Epub 2011 Oct 13.
Arginine vasopressin V(1) receptors have been suggested to be involved in the pathophysiology of acute brain injury. Therefore, we aimed to determine the role of arginine vasopressin V(1) receptors after experimental subarachnoid hemorrhage (SAH).
Sprague-Dawley rats subjected to SAH by endovascular puncture received either vehicle or a V(1) receptor antagonist intravenously from 1 minute before until 3 hours after SAH. Intracranial pressure, cerebral blood flow, and mean arterial blood pressure were monitored until 60 minutes after SAH. Brain water content was quantified 24 hours after SAH and neurological function and mortality were assessed daily for 7 days after hemorrhage.
In control rats, SAH induced high intracranial pressure, a brief increase in plasma arginine vasopressin, a subsequent increase in systemic blood pressure (Cushing response), a high rebleeding rate (30%), severe neurological deficits, and a 7-day mortality rate of 50%. V(1) receptor antagonist-treated animals exhibited a far less pronounced Cushing response, a less severe increase of intracranial pressure, did not exhibit rebleedings, had less severe brain edema formation and neurological deficits, and a mortality rate of only 20% (all P<0.05 versus vehicle).
Inhibition of arginine vasopressin V(1a) receptors reduces the severity of SAH and prevents rebleedings by blunting the posthemorrhagic hypertonic response (Cushing reflex), thereby reducing mortality and secondary brain damage after experimental SAH. Because the severity of the initial bleeding and rebleedings are major factors contributing to an unfavorable outcome after SAH, inhibition of V(1a) receptors may represent a novel strategy to treat SAH.
精氨酸加压素 V1 受体（arginine vasopressin V1 receptors）被认为参与了急性脑损伤的病理生理学过程。因此，我们旨在确定实验性蛛网膜下腔出血（subarachnoid hemorrhage，SAH）后精氨酸加压素 V1 受体的作用。
通过血管内穿刺使 Sprague-Dawley 大鼠发生 SAH，SAH 前 1 分钟至 SAH 后 3 小时内，通过静脉给予载体或 V1 受体拮抗剂。监测颅内压、脑血流和平均动脉血压，直至 SAH 后 60 分钟。SAH 后 24 小时测量脑水含量，并在出血后 7 天内每天评估神经功能和死亡率。
在对照组大鼠中，SAH 引起颅内压升高、血浆精氨酸加压素短暂升高、随后全身血压升高（Cushing 反应）、高再出血率（30%）、严重的神经功能缺损和 7 天死亡率为 50%。V1 受体拮抗剂治疗的动物表现出明显较轻的 Cushing 反应、颅内压升高较轻、无再出血、脑水肿形成和神经功能缺损较轻，死亡率仅为 20%（与载体相比，均 P<0.05）。
抑制精氨酸加压素 V1a 受体可减轻 SAH 的严重程度，通过减弱出血后高渗反应（Cushing 反射）预防再出血，从而降低实验性 SAH 后的死亡率和继发性脑损伤。由于初始出血和再出血的严重程度是影响 SAH 后预后的主要因素，因此抑制 V1a 受体可能是治疗 SAH 的一种新策略。
