Dd. Lund et al., Gene transfer of endothelial nitric oxide synthase improves relaxation of carotid arteries from diabetic rabbits, CIRCULATION, 101(9), 2000, pp. 1027-1033
Citations number
35
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Diabetes mellitus is associated with impairment of NO-mediated v
ascular relaxation. The purpose of this study was to determine whether aden
ovirus-mediated gene transfer of endothelial NO synthase (eNOS) or Cu/Zn su
peroxide dismutase (SOD1) improves responsiveness to acetylcholine in allox
an-induced diabetic rabbits.
Methods and Results-After 8 weeks, plasma glucose was greater in diabetic r
abbits (418+/-135 mg/dL) (mean+/-SEM) than in normal rabbits (105+/-4 mg/dL
). Carotid arteries were removed and cut into ring segments. Arteries were
incubated for 2 hours with adenoviral vectors driven by a CMV promoter expr
essing beta-galactosidase (beta-gal), eNOS, SOD1, or vehicle. After incubat
ion with virus, arteries were incubated for an additional 24 hours to allow
transgene expression. Vascular reactivity was examined by recording isomet
ric tension. After precontraction with phenylephrine, responses to the endo
thelium-independent vasodilator sodium nitroprusside were similar in diabet
ic and normal arteries. Endothelium-dependent relaxation to acetylcholine (
3 X 10(-6) mol/L) was significantly less in arteries from diabetic animals
(68+/-5%) than in normal vessels (90+/-3%). Adenoviral transfection of arte
ries with eNOS improved relaxation in response to acetylcholine in diabetic
(EC50 eNOS = 0.64 +/- 0.12 X 10(-7) mol/L versus vehicle = 1.70 +/- 0.43 x
10(-7) mol/L) but not normal arteries. Vasorelaxation in response to acety
lcholine was inhibited by N-omega-nitro-L-arginine (100 mu mol/L) in all gr
oups. Responses to acetylcholine were unchanged after gene transfection of
SOD1 or P-gal in arteries from diabetic or normal rabbits.
Conclusions-Adenovirus-mediated gene transfer of eNOS, but not SOD, improve
s impaired NO-mediated relaxation in vessels from diabetic rabbits.