Ex vivo gene transfer of endothelial nitric oxide synthase to atherosclerotic rabbit aortic rings improves relaxations to acetylcholine.
Cholesterol feeding results in impaired endothelium dependent vasorelaxation. The role of nitric oxide in this process is unclear. The aim of this study was to evaluate the role of nitric oxide in cholesterol-induced vasomotor dysfunction by examining the effect of overexpression of eNOS in the hypercholesterolemic rabbit aorta on vascular reactivity. Vascular rings from the thoracic aorta of hypercholesterolemic rabbits were exposed ex vivo either to an adenoviral vector encoding endothelial nitric oxide synthase (AdeNOS) or Escherichia coli beta Galactosidase (AdbetaGal). Transgene expression was examined by histochemistry for beta galactosidase, immunohistochemistry for eNOS and cyclic GMP measurements and vasomotor studies were performed. Transgene expression was found to localize to the endothelium and adventitia. cGMP levels were significantly greater in AdeNOS compared to AdbetaGal transduced rings. Acetylcholine mediated relaxation was significantly impaired in cholesterol fed rabbits and was markedly improved by overexpression of eNOS. These results suggest that reduced NO bioavailability observed in cholesterol-induced vascular dysfunction can be partially overcome by eNOS gene transfer.
Mozes
G
G
Division of Vascular Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Kullo
I J
IJ
Mohacsi
T G
TG
Cable
D G
DG
Spector
D J
DJ
Crotty
T B
TB
Gloviczki
P
P
Katusic
Z S
ZS
O'Brien
T
T
D000109:Acetylcholine / Q000494:pharmacology*; D000256:Adenoviridae; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology*; D004926:Escherichia coli; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001616:beta-Galactosidase; D006152:Cyclic GMP; D000109:Acetylcholine