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

Publication ,  Journal Article
Gaballa, MA; Peppel, K; Lefkowitz, RJ; Aguirre, M; Dolber, PC; Pennock, GD; Koch, WJ; Goldman, S
Published in: J Mol Cell Cardiol
May 1998

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.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

May 1998

Volume

30

Issue

5

Start / End Page

1037 / 1045

Location

England

Related Subject Headings

  • beta-Galactosidase
  • Vasodilation
  • Receptors, Adrenergic, beta-2
  • Rats, Sprague-Dawley
  • Rats
  • Muscle, Smooth, Vascular
  • Immunohistochemistry
  • Humans
  • Genetic Vectors
  • Genetic Code
 

Citation

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Gaballa, M. A., Peppel, K., Lefkowitz, R. J., Aguirre, M., Dolber, P. C., Pennock, G. D., … Goldman, S. (1998). Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries. J Mol Cell Cardiol, 30(5), 1037–1045. https://doi.org/10.1006/jmcc.1998.0668
Gaballa, M. A., K. Peppel, R. J. Lefkowitz, M. Aguirre, P. C. Dolber, G. D. Pennock, W. J. Koch, and S. Goldman. “Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries.J Mol Cell Cardiol 30, no. 5 (May 1998): 1037–45. https://doi.org/10.1006/jmcc.1998.0668.
Gaballa MA, Peppel K, Lefkowitz RJ, Aguirre M, Dolber PC, Pennock GD, et al. Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries. J Mol Cell Cardiol. 1998 May;30(5):1037–45.
Gaballa, M. A., et al. “Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries.J Mol Cell Cardiol, vol. 30, no. 5, May 1998, pp. 1037–45. Pubmed, doi:10.1006/jmcc.1998.0668.
Gaballa MA, Peppel K, Lefkowitz RJ, Aguirre M, Dolber PC, Pennock GD, Koch WJ, Goldman S. Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries. J Mol Cell Cardiol. 1998 May;30(5):1037–1045.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

ISSN

0022-2828

Publication Date

May 1998

Volume

30

Issue

5

Start / End Page

1037 / 1045

Location

England

Related Subject Headings

  • beta-Galactosidase
  • Vasodilation
  • Receptors, Adrenergic, beta-2
  • Rats, Sprague-Dawley
  • Rats
  • Muscle, Smooth, Vascular
  • Immunohistochemistry
  • Humans
  • Genetic Vectors
  • Genetic Code