Gene transfer of endothelial nitric oxide synthase (eNOS) in eNOS-deficient mice

Kristy D Lake-Bruse; Frank M Faraci; Edward G Shesely; Nobuyo Maeda; Curt D Sigmund; Donald D Heistad

doi:10.1152/ajpheart.1999.277.2.H770

Back

Gene transfer of endothelial nitric oxide synthase (eNOS) in eNOS-deficient mice

Journal article

Open access

Peer reviewed

Gene transfer of endothelial nitric oxide synthase (eNOS) in eNOS-deficient mice

Kristy D Lake-Bruse, Frank M Faraci, Edward G Shesely, Nobuyo Maeda, Curt D Sigmund and Donald D Heistad

American journal of physiology. Heart and circulatory physiology, Vol.277(2), pp.H770-H776

08/01/1999

DOI: 10.1152/ajpheart.1999.277.2.H770

PMID: 10444505

Files and links (1)

url

https://doi.org/10.1152/ajpheart.1999.277.2.H770View

Published (Version of record) Open Access

Abstract

Relaxation to acetylcholine (ACh) and calcium ionophore (A-23187) is absent in aortas from endothelial nitric oxide synthase (eNOS)-deficient (eNOS -/-) mice. We hypothesized that gene transfer of eNOS would restore relaxation to ACh and A-23187 in eNOS -/- mice. Aortic rings from eNOS -/- and eNOS +/+ mice were exposed in vitro to vehicle or adenoviral vectors encoding β-galactosidase (lacZ) or eNOS. Histochemical staining for β-galactosidase and eNOS demonstrated transduction of endothelial cells and adventitia. Vehicle-treated vessels from eNOS -/- mice did not relax to ACh or A-23187 compared with eNOS +/+ mice. In contrast, relaxation to nitroprusside (NP) was significantly greater in eNOS -/- mice than in eNOS +/+ mice. Gene transfer of eNOS, but not lacZ, to vascular rings of eNOS -/- mice restored relaxation to ACh and A-23187. In vessels from eNOS -/- mice that were transduced with eNOS, N ω-nitro-l-arginine (10−4 M) inhibited relaxation to ACh and A-23187 but not NP. Thus vascular function can be significantly improved by gene transfer in vessels where a major relaxation mechanism is genetically absent.

Details

Title: Subtitle: Gene transfer of endothelial nitric oxide synthase (eNOS) in eNOS-deficient mice
Creators: Kristy D Lake-Bruse - Departments of Internal Medicine, Pharmacology, and Physiology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, Iowa City, Iowa, 52242
Frank M Faraci - Departments of Internal Medicine, Pharmacology, and Physiology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, Iowa City, Iowa, 52242
Edward G Shesely - Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Michigan 48202; and
Nobuyo Maeda - Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599
Curt D Sigmund - Departments of Internal Medicine, Pharmacology, and Physiology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine, Iowa City, Iowa, 52242
Donald D Heistad
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.277(2), pp.H770-H776
DOI: 10.1152/ajpheart.1999.277.2.H770
PMID: 10444505
NLM abbreviation: Am J Physiol Heart Circ Physiol
ISSN: 0363-6135
eISSN: 1522-1539
Language: English
Date published: 08/01/1999
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040331602771

Metrics

10 Record Views

49 Times Cited - Web of Science