Modulation of dilator responses of cerebral arterioles by extracellular superoxide dismutase.
OBJECTIVE
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 micromol/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.
Kitayama
Jiro
J
Cardiovascular Center and Department of Internal Medicine, University of Iowa Carver College of Medicine and VA Medical Center, Iowa City, Iowa 52242-1081, USA.
Yi
Chu
C
Faraci
Frank M
FM
Heistad
Donald D
DD
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D013482:Superoxide Dismutase