Key result
Expression of recombinant iNOS in isolated canine cerebral arteries significantly reduced vasomotor reactivity to both vasoconstrictor and vasodilator agonists (P<0.05).
p-value: p=<0.05
Expression of recombinant iNOS in cerebral arteries reduces vasomotor reactivity to both vasoconstrictor and vasodilator agonists.
May blunt cerebral vasomotor tone in vivo; leaves open relevance to human cerebrovascular disease.
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 degrees C) to an adenoviral vector [10(7), 10(8), or 10(9) plaque-forming units (pfu)/ml] encoding either the iNOS gene or the beta-galactosidase reporter gene. Twenty-four hours after transduction, Western blot analysis demonstrated expression of iNOS protein only in iNOS (10(9) 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 (10(9) pfu/ml)-transduced rings compared with control and beta-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(2)(-).) production were elevated in iNOS-transduced rings (P < 0.05, n = 7 for cGMP; P < 0.01, n = 6-9 for O(2)(-). production). Our results suggest that expression of recombinant iNOS in cerebral arteries reduces vasomotor reactivity to both vasoconstrictor and vasodilator agonists. Attenuation of contractions is most likely due to functional antagonism between UTP and cGMP. Reduction of endothelium-dependent relaxation to bradykinin appears to be mediated in part by reduced reactivity of smooth muscle cells to NO.
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Eguchi et al. (2002) studied Vasomotor function in cerebral arteries. Adenoviral vector encoding the iNOS gene vs. Control and beta-galactosidase-transduced rings was evaluated on Vascular reactivity (concentration-response to UTP and diethylaminodiazen-1-ium-1,2-dioate) (p=<0.05). Expression of recombinant iNOS in isolated canine cerebral arteries significantly reduced vasomotor reactivity to both vasoconstrictor and vasodilator agonists (P<0.05).
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