Angiotensin II increases superoxide production in human arteries

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
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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