Adventitial gene transfer of recombinant endothelial nitric oxide synthase to rabbit carotid arteries alters vascular reactivity

Adventitial gene transfer may serve as a tool to study vascular biology and may have therapeutic potential. We investigated the hypothesis that adenovirus-mediated transfer of the gene for endothelial nitric oxide synthase (eNOS) to the adventitia would alter vascular reactivity. Rabbit carotid arteries were surgically isolated and adenoviral vectors encoding eNOS (AdeNOS) or beta-galactosidase instilled into the periarterial sheath at a concentration of 1 x 10(10) pfu/mL. Arteries were harvested 4 days later for immunostaining, NOS enzymatic assay, measurement of cGMP, and vasomotor studies. Transgene expression in the adventitia was confirmed by histochemistry for beta-galactosidase and immunostaining for eNOS with a monoclonal antibody. Calcium-dependent NOS enzymatic activity and cGMP levels were significantly greater in the AdeNOS-transduced arteries. Maximal contractions to phenylephrine (10(-5) mol/L) were diminished in the AdeNOS-transduced arteries (4.6+/-0.2 versus 5.6+/-0.2 g; P