Journal article
Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD
American journal of physiology. Heart and circulatory physiology, Vol.281(4), pp.H1697-H1703
10/01/2001
DOI: 10.1152/ajpheart.2001.281.4.H1697
PMID: 11557560
Abstract
The goal of this study was to examine the role of endogenous copper/zinc (CuZn)-superoxide dismutase (SOD) on superoxide levels and on responses of cerebral blood vessels to stimuli that are mediated by nitric oxide (acetylcholine) and cyclooxygenase-dependent mechanisms (bradykinin and arachidonic acid). Levels of superoxide in the rabbit basilar artery were measured using lucigenin-enhanced chemiluminescence (5 μM lucigenin). Diethyldithiocarbamate (DDC; 10 mM), an inhibitor of CuZn-SOD, increased superoxide levels by ∼2.4-fold ( P < 0.05) from a baseline value of 1.0 ± 0.2 relative light units · min−1 · mm−2(means ± SE). The diameter of cerebral arterioles (baseline diameter, 99 ± 3 μm) was also measured using a closed cranial window in anesthetized rabbits. Topical application of DDC attenuated responses to acetylcholine, bradykinin, and arachidonate, but not nitroprusside. For example, 10 μM arachidonic acid dilated cerebral arterioles by 40 ± 5 and 2 ± 2 μm under control conditions and after DDC, respectively ( P < 0.05). These inhibitory effects of DDC were reversed by the superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (10 mM). Arachidonate increased superoxide levels in the basilar artery moderately under normal conditions and this increase was greatly augmented in the presence of DDC. These findings suggest that endogenous CuZn-SOD limits superoxide levels under basal conditions and has a marked influence on increases in superoxide in vessels exposed to arachidonic acid. The results also suggest that nitric oxide- and cyclooxygenase-mediated responses in the cerebral microcirculation are dependent on normal activity of CuZn-SOD.
Details
- Title: Subtitle
- Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD
- Creators
- Sean P Didion - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242Christopher A Hathaway - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242Frank M Faraci - Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.281(4), pp.H1697-H1703
- DOI
- 10.1152/ajpheart.2001.281.4.H1697
- PMID
- 11557560
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 10/01/2001
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040216902771
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