Journal article
Gene transfer of calcitonin gene-related peptide prevents vasoconstriction after subarachnoid hemorrhage
Circulation research, Vol.87(9), pp.818-824
2000
DOI: 10.1161/01.RES.87.9.818
PMID: 11055987
Abstract
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.
Details
- Title: Subtitle
- Gene transfer of calcitonin gene-related peptide prevents vasoconstriction after subarachnoid hemorrhage
- Creators
- Kazunori TOYODA - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesFrank M FARACI - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesYoshimasa WATANABE - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesToshihiro UEDA - Department of Radiology, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesJon J ANDRESEN - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesYi CHU - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesShoichiro OTAKE - Department of Radiology, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United StatesDonald D HEISTAD - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.87(9), pp.818-824
- Publisher
- Lippincott; Hagerstown, MD
- DOI
- 10.1161/01.RES.87.9.818
- PMID
- 11055987
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 2000
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040600102771
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