Superoxide levels and function of cerebral blood vessels after inhibition of CuZn-SOD
| Autor: | Sean P. Didion, Christopher A. Hathaway, Frank M. Faraci |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Physiology Vasodilator Agents Hemodynamics Bradykinin Microcirculation Nitric oxide Superoxide dismutase chemistry.chemical_compound Superoxides Physiology (medical) Internal medicine medicine Animals Enzyme Inhibitors Arachidonic Acid biology Superoxide Superoxide Dismutase Acetylcholine Vasodilation Vasomotor System Arterioles Endocrinology Biochemistry chemistry Basilar Artery Cerebrovascular Circulation Circulatory system biology.protein Dismutase Endothelium Vascular Rabbits Cardiology and Cardiovascular Medicine Ditiocarb |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 281(4) |
| ISSN: | 0363-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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