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Vasopressin V1a Receptors Mediate Posthemorrhagic Systemic Hypertension Thereby Determining Rebleeding Rate and Outcome After Experimental Subarachnoid Hemorrhage.
MedLine Citation:
PMID:  21998059     Owner:  NLM     Status:  Publisher    
BACKGROUND AND PURPOSE: 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). METHODS: 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. 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%. 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). CONCLUSIONS: 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.
Konstantin Hockel; Karsten Schöller; Raimund Trabold; Jürg Nussberger; Nikolaus Plesnila
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-13
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  -     ISSN:  1524-4628     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
From the Department of Neurosurgery and the Institute for Surgical Research, University of Munich Medical Center-Grosshadern, Ludwig-Maximilians-University, Munich, Germany; Institute for Stroke and Dementia Research, University of Munich Medical Center, Munich, Germany; Division of Angiology & Hypertension, Centre Hospitalier Universitaire Vaudois and Lausanne University, Lausanne, Switzerland; and the Royal College of Surgeons in Ireland, Dublin, Ireland.
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