Berry, C., Brosnan, M.J., Alexander, Y.M., Hamilton, C.A., Dominiczak, A.F. and McMurray, J.J.V. (2000) Angiotensin II increases superoxide production in human arteries. Heart, 83(S1), p. 6.
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Abstract
Background: Increased vascular superoxide (O2 -) production contributes to endothelial dysfunction and vascular hypertrophy. We investigated whether, and by what mechanisms, angiotensin II (AII) might increase O2 - production in blood vessels. Methods: Internal mammary arteries (IMA) and saphenous veins (SV) were collected from patients undergoing coronary revascularisation surgery. Five mm rings were incubated in the absence (control) or presence 1 μmol/L of AII, or 1 μmol/L of norepinephrine (NE, positive control) for 4 hours. All-incubated rings were co-incubated with an NADH oxidase inhibitor, diphenyleneiodonium (DPI, 100 μmol/L) or a specific All type 1 (AT1) receptor antagonist, losartan (1 μmol/L). O2 - production was measured by lucigenin chemiluminescence. Identification of NADH oxidase within IMA and SV was undertaken using specific antibodies to its active subunits (p22 and p91 phox). Results: All increased O2 - production in IMA (control=978±117 pmol/min/mg, AII 1690±213 pmol/min/mg; n=27, p<0.0001) but not in SV (n=8). NE had no effect on O2 - production in either IMA (control 731±323 pmol/min/mg, NE 636±241; n=10, p=0.76), or SV (n=8). Losartan blocked the AII-mediated increase of O2 - production (losartan 947±245 pmol/min/mg, losartan + AII 1037±231 pmol/min/mg; n=11, p=0.15). DPI inhibited the AII mediated increase in O2 - production (DPI 1124±338 pmol/min/mg, AII + DPI 1055±146 pmol/min/mg; n=8, p=0.9). P22 and p91 phox proteins were localised principally within vascular smooth muscle cells. Conclusion: All increases O2 - production in human arteries by an AT1 receptor-specific, NADH oxidase-dependent mechanism. This suggests a novel therapeutic role for AT1 receptor antagonists in reducing oxidative stress in patients with cardiovascular disease.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McMurray, Professor John |
Authors: | Berry, C., Brosnan, M.J., Alexander, Y.M., Hamilton, C.A., Dominiczak, A.F., and McMurray, J.J.V. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Heart |
ISSN: | 1355-6037 |
ISSN (Online): | 1468-201X |
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