ENHANCED VASORELAXATION BY OVEREXPRESSION OF BETA(2)-ADRENERGIC RECEPTORS IN LARGE ARTERIES

This study was designed to determine if adenoviral-mediated delivery o f a transgene encoding the beta(2)-adrenergic receptor (beta(2)-AR) to the carotid arterial wall could result in alterations in in vivo vasc ular function. De-endothelialized rat carotid arteries were infused in vivo with 0.1 mg/ml elastase and adenovirus [6 x 10(9) plaque forming units (PFU)] containing either the marker gene beta-galactosidase (Ad eno-beta-gal), DNA encoding the human beta(2)-AR (Adeno-beta(2)-AR), o r 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 mor phology of the arterial wall. A transfection efficiency of 73% was ach ieved with Adeno-beta-gal (n=3). beta-gal expression was associated wi th infrequent appearance of T and B lymphocytes, or neutrophil infiltr ation. Five days after infection with Adeno-beta(2)-AR, the total beta -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 transm ural pressures from 10-110 mmHg increased (P<0.01) compared to arterie s exposed to control virus (empty adenovirus), n=4; and isoproterenol- stimulated cAMP production was increased by 65% (n=5). Thus, adenovira l-mediated delivery of beta(2)-ARs into large artery walls results in enhanced beta-AR-mediated vasorelaxation via augmentation in cAMP leve ls in vascular smooth muscle cells. (C) 1998 Academic Press Limited.