Document Detail


Gene transfer of extracellular superoxide dismutase reduces arterial pressure in spontaneously hypertensive rats: role of heparin-binding domain.
MedLine Citation:
PMID:  12600899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress may contribute to hypertension. The goals of this study were to determine whether extracellular superoxide dismutase (ECSOD) reduces arterial pressure in spontaneously hypertensive rats (SHR) and whether its heparin-binding domain (HBD), which is responsible for cellular binding, is necessary for the function of ECSOD. Three days after intravenous injection of an adenoviral vector expressing human ECSOD (AdECSOD), mean arterial pressure (MAP) decreased from 165+/-4 mm Hg (mean+/-SE, n=7) to 124+/-3 mm Hg (n=7) in adult anesthetized SHR (P<0.01) but was not altered in normotensive Wistar-Kyoto rats. Cardiac output was not changed in SHR 3 days after AdECSOD. Gene transfer of ECSOD with deletion of the HBD (AdECSODDeltaHBD) had no effect on SHR MAP, even though plasma SOD activity was greater after AdECSODDeltaHBD than after AdECSOD. Immunohistochemistry revealed intense staining for ECSOD in blood vessels and kidneys after AdECSOD but not after AdECSODDeltaHBD. Impaired relaxation of the carotid artery to acetylcholine in SHR was significantly improved after AdECSOD. Cumulative sodium balance in SHR was reduced by AdECSOD compared with AdECSODDeltaHBD. Gene transfer of ECSOD also reduced MAP in conscious SHR, although the effect was not as profound as in anesthetized SHR. In summary, gene transfer of ECSOD, with a strict requirement for its HBD, reduces systemic vascular resistance and arterial pressure in a genetic model of hypertension. This reduction in arterial pressure may be mediated by vasomotor and/or renal mechanisms.
Authors:
Yi Chu; Shinichiro Iida; Donald D Lund; Robert M Weiss; Gerald F DiBona; Yoshimasa Watanabe; Frank M Faraci; Donald D Heistad
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-01-23
Journal Detail:
Title:  Circulation research     Volume:  92     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-07     Completed Date:  2003-03-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  461-8     Citation Subset:  IM    
Affiliation:
Cardiovascular Center and Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Anesthesia
Animals
Binding Sites / genetics
Blood Pressure / physiology*
Cardiac Output / physiology
Consciousness
Gene Therapy / methods
Genetic Vectors / administration & dosage,  genetics
Heparin / metabolism
Humans
Hypertension / genetics,  physiopathology*,  therapy
Injections, Intravenous
Male
Mutation
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Superoxide Dismutase / genetics*,  metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
DK-15843/DK/NIDDK NIH HHS; DK-52617/DK/NIDDK NIH HHS; DK-54759/DK/NIDDK NIH HHS; HL-14388/HL/NHLBI NIH HHS; HL-16066/HL/NHLBI NIH HHS; HL-55006/HL/NHLBI NIH HHS; HL-62984/HL/NHLBI NIH HHS; NS-24621/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
9005-49-6/Heparin; EC 1.15.1.1/Superoxide Dismutase

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