Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries.
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.
Gaballa
M A
MA
Department of Surgery, Duke University, Durham, NC, USA.
Peppel
K
K
Lefkowitz
R J
RJ
Aguirre
M
M
Dolber
P C
PC
Pennock
G D
GD
Koch
W J
WJ
Goldman
S
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D002339:Carotid Arteries / Q000378:metabolism / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D018014:Gene Transfer Techniques; D005815:Genetic Code; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D014664:Vasodilation / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics
D004279:DNA, Viral; D018343:Receptors, Adrenergic, beta-2; D001616:beta-Galactosidase