Heterogeneity of adenovirus-mediated transfer of endothelial nitric oxide synthase gene in isolated canine arteries

The present study was designed to determine efficiency of adenovirus-mediated transfer of endothelial nitric oxide (eNOS) gene in isolated canine basilar, coronary and femoral arteries. Arterial rings were exposed ex vivo (30 min at 37°C) to an adenoviral vector encoding eNOS gene (AdCMVeNOS) or β-galactosidase reporter gene (AdCMVβ-Gal). Twenty-four hours following transduction, transgene expression was evident in adventitia and endothelium. Intensity of β-galactosidase staining and eNOS immunoreactivity was much higher in basilar artery than in coronary and femoral arteries. β-Galactosidase protein levels were significantly higher in basilar artery than in coronary and femoral arteries, In basilar arteries transduced with AdCMVeNOS but not AdCMVβ-Gal, relaxations to low concentrations of bradykinin (10¹⁰ - 3×10⁹ mol/L) were significantly augmented. In contrast, in coronary and femoral arteries exposed to AdCMVeNOS, relaxations to bradykinin were not affected. Augmentation of relaxations to bradykinin in basilar artery transduced with AdCMVeNOS was completely blocked by a nitric oxide synthase inhibitor, L-NAME. These results demonstrate higher efficiency of adenovirus-mediated gene transfer in cerebral arteries than in peripheral blood vessels. They also suggest that expression of recombinant eNOS gene could be used to increase local production of NO in cerebral arterial wall.