Journal article
Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats: Role of Heparin-Binding Domain
Circulation research, Vol.92(4), pp.461-468
03/07/2003
DOI: 10.1161/01.RES.0000057755.02845.F9
PMID: 12600899
Abstract
ABSTRACT—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 (AdECSODΔHBD) had no effect on SHR MAP, even though plasma SOD activity was greater after AdECSODΔHBD than after AdECSOD. Immunohistochemistry revealed intense staining for ECSOD in blood vessels and kidneys after AdECSOD but not after AdECSODΔHBD. 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 AdECSODΔHBD. 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.
Details
- Title: Subtitle
- Gene Transfer of Extracellular Superoxide Dismutase Reduces Arterial Pressure in Spontaneously Hypertensive Rats: Role of Heparin-Binding Domain
- Creators
- Yi Chu - From the Cardiovascular Center and Departments of Internal Medicine (Y.C., S.I., D.D.L., R.M.W., G.F.D., Y.W., F.M.F., D.D.H.), Pharmacology (F.M.F., D.D.H.), and Physiology (G.F.D.), University of Iowa Roy J. and Lucille A. Carver College of Medicine, and VA Medical Center (D.D.L., R.M.W., G.F.D., D.D.H.), Iowa City, IowaShinichiro IidaDonald LundRobert WeissGerald DiBonaYoshimasa WatanabeFrank FaraciDonald Heistad
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.92(4), pp.461-468
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/01.RES.0000057755.02845.F9
- PMID
- 12600899
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 03/07/2003
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040472002771
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