Effects of extracellular superoxide dismutase on cerebrovascular function

Background Extracellular superoxide dismutase (ecSOD) is abundant in the wall of blood vessels. Effects of ecSOD deficiency on cerebrovascular function are not fully elucidated. The aim of this study was to examine the role of ecSOD in modulation of vasomotor function of cerebral arterioles. Methods Responses of cerebral arterioles (diameter 26±1 μm) in ecSOD knockout (KO) mice were examined using a cranial window in anesthetized, ventilated mice. Wild‐type (WT) littermate mice were used as control. Results Total SOD activity of aorta in ecSOD KO mice was 23 % lower than in WT mice. Dilator responses to acetylcholine were similar in ecSOD WT and KO mice (34±5 [mean±SE] vs. 32±4 % to 10 μM of acetylcholine). During superfusion of angiotensin II (500 nM for 30 min), dilator responses to acetylcholine tended to be reduced in WT mice (to 28±6; n.s.). In ecSOD KO mice, acetylcholine‐induced dilatation was impaired significantly (to 18±4; * p =0.01) (Figure). Nitroprusside‐induced dilator responses were not affected by angiotensin II in ecSOD KO and WT mice. In the presence of the superoxide scavenger tempol (1 mM for 30 min) and angiotensin II, dilator responses to acetylcholine were restored in ecSOD KO mice (to 30±4 %). Conclusions These results indicate that lack of ecSOD does not impair endothelial function under baseline conditions. Endogenous ecSOD, however, protects cerebral arterioles against oxidative stress induced by angiotensin II, and helps to preserve endothelial function.