Gene transfer of endothelial nitric oxide synthase (eNOS) in eNOS-deficient mice. Am J Physiol 1999 Aug;277(2):H770-6
Date
08/13/1999Pubmed ID
10444505DOI
10.1152/ajpheart.1999.277.2.H770Scopus ID
2-s2.0-0032879970 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
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 beta-galactosidase (lacZ) or eNOS. Histochemical staining for beta-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(omega)-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.
Author List
Lake-Bruse KD, Faraci FM, Shesely EG, Maeda N, Sigmund CD, Heistad DDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenoviridaeAnimals
Aorta
Endothelium, Vascular
Female
Gene Transfer Techniques
Genetic Vectors
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Recombinant Proteins
Vasomotor System
