© 1998 American Heart Association, Inc.
Original Contributions |
Ascorbate Prevents the Interaction of Superoxide and Nitric Oxide Only at Very High Physiological Concentrations
From the Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.
Correspondence to John F. Keaney, Jr, MD, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St, Room W507, Boston, MA 02118. E-mail jkeaney{at}bu.edu
Abstract—The bioactivity of
nitric oxide (
NO) depends, in part, on its interaction
with superoxide. Usually, superoxide dismutase (SOD) preserves
NO bioactivity by limiting the availability of
superoxide. Ascorbic acid also effectively scavenges superoxide, but
the extent to which this interaction is necessary for intact
NO bioactivity is not known. Therefore, the present
study examined the effect of ascorbic acid on NO
bioactivity with isolated rabbit arterial segments. A
steady flux of superoxide (1.15 to 2.3 µmol ·
L-1 · min-1) produced either by
pyrogallol autoxidation or a hypoxanthine/xanthine oxidase system
inhibited endothelium-derived
NO-mediated arterial relaxation elicited by
acetylcholine. This effect of superoxide was completely blocked by SOD
(300 IU/mL) and the manganese SOD mimic EUK-8 (300 µmol/L) and
partially inhibited by ascorbic acid (10 mmol/L). Lower
concentrations of ascorbic acid were ineffective despite scavenging
>90% of superoxide. We increased the endogenous flux of
superoxide (3.2±0.3-fold) by inhibiting vascular copper-zinc SOD with
diethyldithiocarbamate. This increased endogenous flux of
superoxide produced an impairment of NO-mediated
arterial relaxation that was reversed by EUK-8 (300
µmol/L) but not ascorbic acid (10 mmol/L) despite equivalent
scavenging of the endogenous superoxide flux. We used
3-nitrotyrosine formation (from peroxynitrite) as an indicator of
NO interaction with superoxide and found that SOD and
EUK-8 compete more effectively with NO for superoxide
than does ascorbic acid. These data indicate that preservation of
NO bioactivity by superoxide scavengers depends not only
on superoxide scavenging activity, but also on the rate of superoxide
scavenging. Normal extracellular concentrations of ascorbic acid (30 to
150 µmol/L) are not likely to prevent the interaction of
NO with superoxide under physiological conditions.
Key Words: antioxidant • free radical • blood vessel • oxidant • peroxynitrite
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|
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|
|
|
|
|
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