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Modulation of dilator responses of cerebral arterioles by extracellular superoxide dismutase
Journal article   Open access   Peer reviewed

Modulation of dilator responses of cerebral arterioles by extracellular superoxide dismutase

Jiro KITAYAMA, Chu Yi, Frank M FARACI and Donald D HEISTAD
Stroke (1970), Vol.37(11), pp.2802-2806
2006
DOI: 10.1161/01.STR.0000245134.12145.ae
PMID: 17008608
url
https://doi.org/10.1161/01.STR.0000245134.12145.aeView
Published (Version of record) Open Access

Abstract

Background and Purpose— Extracellular superoxide dismutase (ECSOD) is highly expressed in the wall of blood vessels and plays an important role in modulation of vascular function in extracranial arteries. Expression of ECSOD appears to affect cerebral vascular responses during disease states. Effects of ECSOD on dilator function in cerebral arterioles, however, have not been fully elucidated. In the present study, we examined effects of ECSOD deficiency on cerebrovascular reactivity under control conditions and during oxidative stress. Methods— Dilator responses of cerebral arterioles were examined in cranial windows in vivo in anesthetized ECSOD-deficient (−/−) and wild-type (+/+) mice under normal conditions and during oxidative stress induced by angiotensin II. Results— Total SOD activity in the aorta in ECSOD−/− mice (176±24 [mean±SEM] U/mg) was approximately 30% lower than in ECSOD+/+ mice (270±38, P=0.051). Dilator responses to acetylcholine (10 μmol/L) in cerebral arterioles were similar under control conditions in ECSOD+/+ (34±5% changes in diameter) and −/− mice (32±4%). Angiotensin II (500 nmol/L for 30 minutes) tended to reduce responses to acetylcholine in ECSOD+/+ mice (not significant) and significantly impaired responses in ECSOD−/− mice (42% reduction, P<0.05). Tempol (1 mmol/L), a scavenger of superoxide, restored the impaired dilator responses in ECSOD−/− mice. Responses to nitroprusside in cerebral arterioles were similar in ECSOD+/+ and −/− mice and were not affected by angiotensin II nor by tempol. Conclusions— ECSOD deficiency has little effect on cerebrovascular reactivity in control conditions but plays an important role in the regulation of vascular tone during oxidative stress produced by angiotensin II.
 Biotechnology Neurology Gene Therapy Fundamental and applied biological sciences. Psychology Vertebrates: nervous system and sense organs Health. Pharmaceutical industry Industrial applications and implications. Economical aspects Biological and medical sciences Vascular diseases and vascular malformations of the nervous system Medical sciences Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges

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