VASOMOTOR DYSFUNCTION EARLY AFTER EXPOSURE OF NORMAL RABBIT ARTERIES TO AN ADENOVIRAL VECTOR

We aimed to investigate whether infection of normal rabbit arteries wi th a recombinant adenovirus vector would result per se in alterations in contractile and endothelial functions, In one group of rabbits, rig ht or left femoral and ear artery segments were injected in vivo with a replication-deficient adenoviral vector expressing a beta-galactosid ase (beta-Gal) reporter gene (4 x 10(10) pfu/ml) to demonstrate effici ent gene transfer. Contralateral arteries were injected with the same concentration of a recombinant adenoviral vector carrying no transgene (Ad.MLPnull). In another group of animals, Ad.MLPnull was injected in to the lumen of femoral and ear artery segments, The contralateral art eries were used as controls with the injection of vehicle alone, Histo chemical assessment of gene transfer using beta-Gal activity (group 1) or in vitro contractility and endothelial function (group 2) was perf ormed 3 days after adenoviral infection, Gene transfer was efficient a nd reproducible in the endothelium and was associated with the presenc e of inflammatory cells in the media, In Ad.MLPnull-injected arteries, in vitro contractile response of femoral artery rings to either KCl 6 0 mM or phenylephrine (10 mu M) was reduced to 10.5 +/- 2.3% (n = 14; p < 0.001) and 8.8 +/- 2.0% (n = 7; p < 0.001) of the control values, respectively, Furthermore, in arteries injected with Ad.MLPnull, the e ndothelium-dependent relaxation produced by acetylcholine (10 mu M) wa s virtually abolished, Similarly, the relaxant effects of the alpha(2) -adrenoreceptor agonist UK14304 (1 mu M) or the Ca2+ ionophore A23187 (1 mu M) were also abolished, By contrast, sodium nitroprusside (10 mu M) was still able to relax adenovirus-infected arteries, We conclude that infection with a recombinant adenoviral vector can induce early s evere vasomotor alterations in both contractile function and endotheli um-mediated relaxation off normal rabbit arteries.