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 vasorelaxatio n. The role of nitric oxide in this process is unclear. The aim of this stu dy was to evaluate the role of nitric oxide in cholesterol-induced vasomoto r dysfunction by examining the effect of overexpression of eNOS in the hype rcholesterolemic rabbit aorta on vascular reactivity. Vascular rings from t he thoracic aorta of hypercholesterolemic rabbits were exposed ex vivo eith er to an adenoviral vector encoding endothelial nitric oxide synthase (AdeN OS) or Escherichia coli beta Galactosidase (Ad beta Gal). Transgene express ion was examined by histochemistry for beta galactosidase, immunohistochemi stry for eNOS and cyclic GMP measurements and vasomotor studies were perfor med. Transgene expression was found to localize to the endothelium and adve ntitia. cGMP levels were significantly greater in AdeNOS compared to Ad bet a Gal transduced rings. Acetylcholine mediated relaxation was significantly impaired in cholesterol fed rabbits and was markedly improved by overexpre ssion of eNOS. These results suggest that reduced NO bioavailability observ ed in cholesterol-induced vascular dysfunction can be partially overcome by eNOS gene transfer. (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.