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 micromol . 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 micromol/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 micromol/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 micromol/L) are not likely to prevent the interaction of .NO with superoxide under physiological conditions.
journal_name
Circ Resjournal_title
Circulation researchauthors
Jackson TS,Xu A,Vita JA,Keaney JF Jrdoi
10.1161/01.res.83.9.916subject
Has Abstractpub_date
1998-11-02 00:00:00pages
916-22issue
9eissn
0009-7330issn
1524-4571journal_volume
83pub_type
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