Journal article
Altered vascular function after adenovirus-mediated overexpression of endothelial nitric oxide synthase
American journal of physiology. Heart and circulatory physiology, Vol.273(1), pp.H265-H270
07/01/1997
DOI: 10.1152/ajpheart.1997.273.1.H265
PMID: 9249499
Abstract
Gene transfer with replication-deficient adenovirus is a potentially useful tool to study vascular biology. We have constructed a replication-deficient adenovirus (AdRSVeNOS) that carries cDNA for endothelial nitric oxide synthase (eNOS). Transfection of COS-1 cells with AdRSVeNOS increased nitric oxide synthase activity (measured as production of L-citrulline from L-arginine) that was calcium dependent and inhibited by N omega-nitro-L-arginine methyl ester. To investigate effects of overexpression of eNOS on vascular function, we incubated common carotid arteries from rabbits in organ culture with AdRSVeNOS or AdRSV beta gal encoding beta-galactosidase. Transgene expression and responses to vasoactive agents were examined 1 day after transduction. Histochemical staining of beta-galactosidase and immunohistochemistry for eNOS indicated transgene expression in endothelium and adventitial cells. After precontraction with phenylephrine, vessels treated with AdRSVeNOS demonstrated greater relaxation to acetylcholine than vessels treated with vehicle or AdRSV beta gal. Relaxation to calcium ionophore A-23187 was much greater in vessels treated with AdRSVeNOS than in vessels treated with vehicle or AdRSV beta gal. Augmented relaxation in response to A-23187 was also observed after denudation of endothelium in vessels treated with AdRSVeNOS and was inhibited by N omega-nitro-L-arginine. Thus vasorelaxation in response to stimuli that release nitric oxide is augmented after adenovirus-mediated overexpression of eNOS. Transgene expression in adventitial cells appears to be sufficient to alter vasomotor function.
Details
- Title: Subtitle
- Altered vascular function after adenovirus-mediated overexpression of endothelial nitric oxide synthase
- Creators
- Hiroaki Ooboshi - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USAYi Chu - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USAC. David Rios - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USAFrank M Faraci - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USABeverly L Davidson - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USADonald D Heistad - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.273(1), pp.H265-H270
- DOI
- 10.1152/ajpheart.1997.273.1.H265
- PMID
- 9249499
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 07/01/1997
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040358602771
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