Enhanced Vasorelaxation by Overexpression ofβ2-adrenergic Receptors in Large Arteries

This study was designed to determine if adenoviral-mediated delivery of a transgene encoding theβ2-adrenergic receptor (β2-AR) to the carotid arterial wall could result in alterations inin vivovascular function. De-endothelialized rat carotid arteries were infusedin vivowith 0.1 mg/ml elastase and adenovirus [6×109plaque forming units (PFU)] containing either the marker geneβ-galactosidase (Adeno-β-gal), DNA encoding the humanβ2-AR (Adeno-β2-AR), or no transgene. This low concentration of elastase increased the water permeability (5.2±0.6v1.9±0.4×10−8cm/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 totalβ-AR density increased six-fold (67.8±3.4v397.0±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 ofβ2-ARs into large artery walls results in enhancedβ-AR-mediated vasorelaxation via augmentation in cAMP levels in vascular smooth muscle cells.