Gene transfer of endothelial nitric oxide synthase (eNOS) in eNOS-deficient mice.
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.
Lake-Bruse
K D
KD
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA.
Faraci
F M
FM
Shesely
E G
EG
Maeda
N
N
Sigmund
C D
CD
Heistad
D D
DD
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000821:virology; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011994:Recombinant Proteins / Q000378:metabolism; D014666:Vasomotor System / Q000503:physiopathology
D011994:Recombinant Proteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse