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1 Departments of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905; 2 Gene Vec, Incorporated, Gaithersburg, Maryland 20878; and 3 Department of Medicine, Clinical Sciences Institute, University College Hospital, Galway, Ireland
The present study was designed
to determine the effect of recombinant inducible nitric oxide (NO)
synthase (iNOS) gene expression on vasomotor function in cerebral
arteries. Isolated canine basilar arteries were exposed ex vivo (30 min
at 37°C) to an adenoviral vector [107, 108,
or 109 plaque-forming units (pfu)/ml] encoding either the
iNOS gene or the
-galactosidase reporter gene. Twenty-four hours
after transduction, Western blot analysis demonstrated expression of iNOS protein only in iNOS (109 pfu/ml)-transduced arteries.
Immunohistochemical analysis localized iNOS expression predominantly in
adventitia. Vascular reactivity of isolated basilar arteries was
studied by isometric force recording. Concentration-response curves to
UTP (10
9-10
3 M) and
diethylaminodiazen-1-ium-1,2-dioate
(10
10-10
5 M) were
significantly shifted to the right in iNOS gene (109
pfu/ml)-transduced rings compared with control and
-galactosidase-transduced rings (P < 0.05, n = 5-6). Endothelium-dependent relaxation to bradykinin was significantly attenuated in iNOS-transduced rings (P < 0.001, n = 8). The basal level of
cGMP and superoxide anion (O

adventitia; bradykinin; nitric oxide; superoxide anion; inducible nitric oxide synthase
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