Affiliation:
1. From the Department of Medicine and Therapeutics, University of Glasgow, Glasgow, UK.
Abstract
Background
—Increased vascular superoxide anion (·O
2
−
) production contributes to endothelial dysfunction and hypertension in animal models of cardiovascular disease. Observations in experimental animals suggest that angiotensin II (Ang II) increases ·O
2
−
production by activation of vascular NAD(P)H oxidase. We studied the sources of ·O
2
−
production in human blood vessels and investigated whether, and by what mechanism, Ang II might alter vascular ·O
2
−
production.
Methods and Results
—Internal mammary arteries (IMAs) and saphenous veins (SVs) were collected at the time of cardiac surgery. Vessels were incubated in Krebs buffer at 37°C. ·O
2
−
was measured by lucigenin chemiluminescence. Basal ·O
2
−
concentrations were greater in IMAs than SVs. Inhibitors of NAD(P)H oxidase (10 μmol/L to 200 μmol/L diphenyleneiodonium) and xanthine oxidase (1 mmol/L allopurinol) caused reductions in ·O
2
−
concentrations in both IMAs and SVs. Western blotting of superoxide dismutase proteins demonstrated similar expression in IMAs and SVs. Vessels were also incubated in the presence or absence of Ang II (1 pmol/L to 1 μmol/L). Ang II increased ·O
2
−
production in IMAs at 4 hours of incubation (control, 978±117 pmol · min
−1
· mg
−1
; 1 μmol/L of Ang II, 1690±213 pmol · min
−1
· mg
−1
; n=27,
P
=0.0001, 95% CI 336, 925) but not in SVs. This effect was completely inhibited by coincubation of IMAs with DPI (100 μmol/L), a nonspecific Ang II antagonist ([sar
1
, thre
8
]–Ang II, 1 μmol/L) and a specific Ang II type 1 (AT
1
) receptor antagonist (losartan, 1 μmol/L).
Conclusions
— ·O
2
−
production is greater in human IMAs than in SVs. NAD(P)H oxidase and xanthine oxidase are sources of ·O
2
−
production in these vessels. The vasoactive peptide Ang II increases ·O
2
−
production in human arteries by an AT
1
receptor–dependent mechanism.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
271 articles.
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