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

Mohamed A. Gaballa, Karsten Peppel, Robert J. Lefkowitz, Maria Aguirre, Paul C. Dolber, Gregory D. Pennock, Walter J. Koch, Steven Goldman

    Research output: Contribution to journalArticle

    31 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)1037-1045
    Number of pages9
    JournalJournal of Molecular and Cellular Cardiology
    Volume30
    Issue number5
    DOIs
    StatePublished - May 1998

    Keywords

    • Gene transfer
    • Vascular tone
    • β-receptors

    ASJC Scopus subject areas

    • Molecular Biology
    • Cardiology and Cardiovascular Medicine

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    Gaballa, M. A., Peppel, K., Lefkowitz, R. J., Aguirre, M., Dolber, P. C., Pennock, G. D., Koch, W. J., & Goldman, S. (1998). Enhanced vasorelaxation by overexpression of β2-adrenergic receptors in large arteries. Journal of Molecular and Cellular Cardiology, 30(5), 1037-1045. https://doi.org/10.1006/jmcc.1998.0668