Vasopressin V1a Receptors Mediate Posthemorrhagic Systemic Hypertension Thereby Determining Rebleeding Rate and Outcome After Experimental Subarachnoid Hemorrhage
Background and Purpose—Arginine vasopressin V1 receptors have been suggested to be involved in the pathophysiology of acute brain injury. Therefore, we aimed to determine the role of arginine vasopressin V1 receptors after experimental subarachnoid hemorrhage (SAH).
Methods—Sprague-Dawley rats subjected to SAH by endovascular puncture received either vehicle or a V1 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.
Results—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%. V1 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).
Conclusions—Inhibition of arginine vasopressin V1a 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 V1a receptors may represent a novel strategy to treat SAH.
- antidiuretic hormone (ADH)
- arginine vasopressin (AVP)
- brain edema
- Cushing response
- subarachnoid hemorrhage
- V1a receptors
- Received May 14, 2011.
- Revision received June 29, 2011.
- Accepted July 6, 2011.
- © 2011 American Heart Association, Inc.