Journal article
Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP
Cardiovascular research, Vol.47(3), pp.609-617
2000
DOI: 10.1016/S0008-6363(00)00079-1
PMID: 10963734
Abstract
Objective: Previous studies from our group have shown a deficit in nitric oxide (NO) bioavailability and an excess production of the superoxide anion (O2−) in the stroke prone spontaneously hypertensive rat (SHRSP) compared to the normotensive Wistar Kyoto (WKY) strain. This present study has investigated whether adenoviral-mediated gene transfer of human eNOS or Cu/ZnSOD can alter the NO/O2− balance, thereby improving endothelial function. Methods: A recombinant adenovirus, Ad/Hu/eNOS, containing the human eNOS cDNA fragment was generated by homologous recombination in 293 cells. Ad/Hu/eNOS or Ad/Cu/ZnSOD was delivered into SHRSP carotid arteries in vivo, using a titre of 2×109–2×1010 plaque forming units (pfu)/ml, and the effect on gene expression was observed 24 h later. Results: Western blotting confirmed increased enzyme levels of eNOS and Cu/ZnSOD in the viral-infused vessels. Ex vivo, the pressor response to phenylephrine (PE) in the presence of L-NAME was increased in the eNOS-infused arteries relative to the contralateral controls, indicating restoration of basal NO availability to that observed in untreated control WKY rats. Infusion of the SOD virus produced a statistically insignificant increase in NO bioavailability. Conclusions: Our results support our previous findings obtained using a bovine eNOS recombinant adenovirus, that recombinant adenoviral gene transfer of human eNOS has a significant effect on NO bioavailability. In contrast, AdCu/ZnSOD gene transfer does not elicit an effect in our model. These results indicate that short-term overexpression of a recombinant eNOS, but not Cu/ZnSOD gene, in carotid arteries of the SHRSP is an effective means of locally increasing NO bioavailability to improve endothelial function.
Details
- Title: Subtitle
- Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP
- Creators
- M. Y ALEXANDER - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United KingdomM. J BROSNAN - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United KingdomCarlene A Hamilton - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United KingdomJ. P FENNELL - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United KingdomE. C BEATTIE - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United KingdomE JARDINE - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United KingdomD. D HEISTAD - Department of Internal Medicine, University of Iowa, Iowa, IA 52242, United StatesA. F DOMINICZAK - Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Church St., Glasgow G11 6NT, Scotland, United Kingdom
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.47(3), pp.609-617
- Publisher
- Oxford University Press; Oxford
- DOI
- 10.1016/S0008-6363(00)00079-1
- PMID
- 10963734
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Language
- English
- Date published
- 2000
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040450402771
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