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Gene transfer of endothelial nitric oxide synthase improves relaxation of carotid arteries from diabetic rabbits
Journal article   Open access   Peer reviewed

Gene transfer of endothelial nitric oxide synthase improves relaxation of carotid arteries from diabetic rabbits

D. D LUND, F. M FARACI, F. J MILLER and D. D HEISTAD
Circulation (New York, N.Y.), Vol.101(9), pp.1027-1033
2000
DOI: 10.1161/01.CIR.101.9.1027
PMID: 10704171
url
https://doi.org/10.1161/01.CIR.101.9.1027View
Published (Version of record) Open Access

Abstract

Background—Diabetes mellitus is associated with impairment of NO-mediated vascular relaxation. The purpose of this study was to determine whether adenovirus-mediated gene transfer of endothelial NO synthase (eNOS) or Cu/Zn superoxide dismutase (SOD1) improves responsiveness to acetylcholine in alloxan-induced diabetic rabbits. Methods and Results—After 8 weeks, plasma glucose was greater in diabetic rabbits (418±35 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 expressing β-galactosidase (β-gal), eNOS, SOD1, or vehicle. After incubation with virus, arteries were incubated for an additional 24 hours to allow transgene expression. Vascular reactivity was examined by recording isometric tension. After precontraction with phenylephrine, responses to the endothelium-independent vasodilator sodium nitroprusside were similar in diabetic and normal arteries. Endothelium-dependent relaxation to acetylcholine (3×10−6 mol/L) was significantly less in arteries from diabetic animals (68±5%) than in normal vessels (90±3%). Adenoviral transfection of arteries with eNOS improved relaxation in response to acetylcholine in diabetic (EC50 eNOS=0.64±0.12×10−7 mol/L versus vehicle =1.70±0.43×10−7 mol/L) but not normal arteries. Vasorelaxation in response to acetylcholine was inhibited by Nω-nitro-l-arginine (100 μmol/L) in all groups. Responses to acetylcholine were unchanged after gene transfection of SOD1 or β-gal in arteries from diabetic or normal rabbits. Conclusions—Adenovirus-mediated gene transfer of eNOS, but not SOD, improves impaired NO-mediated relaxation in vessels from diabetic rabbits.
 Biological and medical sciences Endocrinopathies Diabetes. Impaired glucose tolerance Medical sciences Endocrine pancreas. Apud cells (diseases) Associated diseases and complications

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