Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries.

Published

Journal Article

This study was designed to determine if adenoviral-mediated delivery of a transgene encoding the beta 2-adrenergic receptor (beta 2-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 10(9) plaque forming units (PFU)] containing either the marker gene beta-galactosidase (Adeno-beta-gal), DNA encoding the human beta 2-AR (Adeno-beta 2-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-beta-gal (n = 3). beta-gal expression was associated with infrequent appearance of T and B lymphocytes, or neutrophil infiltration. 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 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 beta 2-ARs into large artery walls results in enhanced beta-AR-mediated vasorelaxation via augmentation in cAMP levels in vascular smooth muscle cells.

Full Text

Duke Authors

Cited Authors

  • Gaballa, MA; Peppel, K; Lefkowitz, RJ; Aguirre, M; Dolber, PC; Pennock, GD; Koch, WJ; Goldman, S

Published Date

  • May 1998

Published In

Volume / Issue

  • 30 / 5

Start / End Page

  • 1037 - 1045

PubMed ID

  • 9618244

Pubmed Central ID

  • 9618244

International Standard Serial Number (ISSN)

  • 0022-2828

Digital Object Identifier (DOI)

  • 10.1006/jmcc.1998.0668

Language

  • eng

Conference Location

  • England