Document Detail

Gene transfer of calcitonin gene-related peptide prevents vasoconstriction after subarachnoid hemorrhage.
MedLine Citation:
PMID:  11055987     Owner:  NLM     Status:  MEDLINE    
We sought to determine whether adenovirus-mediated gene transfer in vivo of calcitonin gene-related peptide (CGRP), a potent vasodilator, ameliorates cerebral vasoconstriction after experimental subarachnoid hemorrhage (SAH). Arterial blood was injected into the cisterna magna of rabbits to mimic SAH 5 days after injection of AdRSVCGRP (8x10(8) pfu), AdRSVbetagal (control virus), or vehicle. After injection of AdRSVCGRP, there was a 400-fold increase in CGRP in cerebrospinal fluid. Contraction of the basilar artery to serotonin in vitro was greater in rabbits after SAH than after injection of artificial cerebrospinal fluid (P<0.001). Contraction to serotonin was less in rabbits with SAH after AdRSVCGRP than after AdRSVbetagal or vehicle (P:<0.02). Basal diameter of the basilar artery before SAH (measured with digital subtraction angiogram) was 13% greater in rabbits treated with AdRSVCGRP than in rabbits treated with vehicle or AdRSVbetagal (P:<0.005). In rabbits treated with vehicle or AdRSVbetagal, arterial diameter after SAH was 25+/-3% smaller than before SAH (P<0.0005). In rabbits treated with AdRSVCGRP, arterial diameter was similar before and after SAH and was reduced by 19+/-3% (P<0.01) after intracisternal injection of CGRP-(8-37) (0.5 nmol/kg), a CGRP(1) receptor antagonist. To determine whether gene transfer of CGRP after SAH may prevent cerebral vasoconstriction, we constructed a virus with a cytomegalovirus (CMV) promoter, which results in rapid expression of the transgene product. Treatment of rabbits with AdCMVCGRP after experimental SAH prevented constriction of the basilar artery 2 days after SAH. Thus, gene transfer of CGRP prevents cerebral vasoconstriction in vivo after experimental SAH.
K Toyoda; F M Faraci; Y Watanabe; T Ueda; J J Andresen; Y Chu; S Otake; D D Heistad
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  87     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-03     Completed Date:  2000-12-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  818-24     Citation Subset:  IM    
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MeSH Terms
Adenoviridae / genetics
Basilar Artery / drug effects*,  pathology
Calcitonin Gene-Related Peptide / cerebrospinal fluid,  genetics,  therapeutic use*
Gene Therapy / methods*
Gene Transfer Techniques
Injections, Intraventricular
Subarachnoid Hemorrhage / cerebrospinal fluid,  therapy*
Time Factors
Vasodilator Agents / therapeutic use*
Vasospasm, Intracranial / chemically induced,  prevention & control
Grant Support
Reg. No./Substance:
0/Vasodilator Agents; 50-67-9/Serotonin; 51-45-6/Histamine; 83652-28-2/Calcitonin Gene-Related Peptide
Comment In:
Circ Res. 2000 Oct 27;87(9):719-21   [PMID:  11055971 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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