Enhanced vasorelaxation by overexpression of β₂-adrenergic receptors in large arteries

This study was designed to determine if adenoviral-mediated delivery of a transgene encoding the β₂-adrenergic receptor (β₂-AR) to the carotid arterial wall could result in alterations in in vivo vascular function. De-endothelialized rat carotid arteries were infused in vivo with 0.1 mg/ml elastase and adenovirus [6 x 10⁹ plaque forming units (PFU)] containing either the marker gene β-galactosidase (Adeno-β-gal), DNA encoding the human β₂-AR (Adeno-β₂-AR), or no transgene. This low concentration of elastase increased the water permeability (5.2 ± 0.6 v 1.9 ± 0.4 x 10^-8 cm/s/mmHg, n = 4, P < 0.0001) without affecting either the vasomotor responsiveness or the morphology of the arterial wall. A transfection efficiency of 73% was achieved with Adeno-β-gal (n = 3). β-gal expression was associated with infrequent appearance of T and B lymphocytes, or neutrophil infiltration. Five days after infection with Adeno-β₂-AR, the total β-AR density increased six-fold (67.8 ± 3.4 v 397.0 ± 155.5 fmol/mg protein, n = 5, P < 0.01); isoproterenol-induced vasorelaxation at transmural pressures from 10-110 mmHg increased (P < 0.01) compared to arteries exposed to control virus (empty adenovirus), n = 4; and isoproterenol-stimulated cAMP production was increased by 65% (n = 5). Thus, adenoviral-mediated delivery of β₂-ARs into large artery walls results in enhanced β-AR-mediated vasorelaxation via augmentation in cAMP levels in vascular smooth muscle cells.