Journal article
Gene Transfer of Endothelial Nitric Oxide Synthase Reduces Angiotensin II–Induced Endothelial Dysfunction
Hypertension (Dallas, Tex. 1979), Vol.35(2), pp.595-601
02/2000
DOI: 10.1161/01.HYP.35.2.595
PMID: 10679503
Abstract
Angiotensin II stimulates vascular NADPH oxidase to produce superoxide, which can react with nitric oxide and impair vasomotor function. We tested the hypothesis that the overexpression of endothelial nitric oxide synthase (eNOS) or superoxide dismutase (SOD) would correct angiotensin II-induced endothelial dysfunction. We examined the effects of the gene transfer of eNOS or 2 isoforms of SOD to the aorta in angiotensin II-treated rabbits on vasomotor function. New Zealand White rabbits were treated for 1 week with angiotensin II (100 ng. kg(-1). min(-1)) or saline by osmotic minipumps. In angiotensin II-treated rabbits, mean blood pressure was 107+/-8 mm Hg; it was 67+/-5 mm Hg in saline-infused rabbits (P<0.05). In aortas from angiotensin II-treated rabbits, lucigenin-enhanced chemiluminescence demonstrated a 2.5-fold increase in superoxide levels, and the oxidative fluorescent probe hydroethidine indicated increased superoxide levels throughout the vascular wall, especially in the endothelium and adventitia. Maximal relaxation to acetylcholine was less in aortas from rabbits treated with angiotensin II (72+/-5% versus 87+/-4% in saline-treated rabbits; P<0.01), but responses to sodium nitroprusside were similar. Segments of the thoracic aorta were incubated in vitro with an adenoviral vector that expressed eNOS, copper zinc SOD (CuZnSOD), extracellular SOD (ECSOD), or beta-galactosidase. beta-Gal treatment with adenovirus containing the gene for eNOS (AdeNOS) but not adenovirus containing the gene for beta-gal (Adbeta-gal) (control virus) restored responses to acetylcholine (82+/-3% after AdeNOS and 67+/-4% after Adbeta-gal). Gene transfer of CuZnSOD or ECSOD did not improve the endothelium-dependent relaxation of the aorta in rabbits that received angiotensin II. Thus, gene transfer of eNOS, but not SOD, effectively restores vasomotor function in angiotensin II-infused rabbits.
Details
- Title: Subtitle
- Gene Transfer of Endothelial Nitric Oxide Synthase Reduces Angiotensin II–Induced Endothelial Dysfunction
- Creators
- Hiroshi Nakane - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa CityFrancis J Miller - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa CityFrank M Faraci - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa CityKazunori Toyoda - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa CityDonald D Heistad - From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.35(2), pp.595-601
- DOI
- 10.1161/01.HYP.35.2.595
- PMID
- 10679503
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 02/2000
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040592002771
Metrics
11 Record Views