Effects of Amiloride and Na Selenite on the ATPase Levels, Malondialdehyde Levels, and on Superoxide Dismutase Activity and the Histopathologic Findings After Subarachnoid Hemorrhage in the Pigs

摘要

Objectives: Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a reversible arterial narrowing occurring as a result of the mechanical and physiologic effects of blood products. Multiple factors are effective in the development of arterial narrowing; they provide long-term arterial contraction, inhibition of vasodilatation, and depression of the metabolic, immunoreactive, and inflammatory processes. We assessed Na selenite, which activates calpain II and promotes intracellular Ca~(2+) influx, by increasing oxygen radical synthesis in SAH. We also assessed amiloride, which involves non-voltage-graded Na channels, Na~+/Ca~(2+) exchange, and Na~+/H~+ antiport mechanism and antioxidative effects. We evaluated the morphologic and biochemical effects of Na selenite and amiloride on basilar arterial smooth muscle vessels in SAH. Methods: Twenty pigs were randomly allocated to 4 groups. In group 1 only SAH was created. In group 2, after SAH, subcutaneously amiloride was applied once a day for 4 weeks. In group 3, after SAH subcutaneous Na selenite was applied once a day for 4 weeks. In group 4, after SAH, amiloride and Na~+ selenite were given subsequently once a day for 4 weeks. The effects of amiloride and Na selenite on the ATPase and malondialdehyde (MDA) levels, and on Superoxide dismutase activity (SOD), and the resulting histopathologic findings were studied. Results: In group 2, the vessel SOD level was 3 times higher than in group 1, but the Na~+ K~+ ATPase and MDA levels were found to be similar. In group 3, SOD activity was found to be similar to that in group 1. but Na~+ K~+ ATPase and MDA levels were 3 times higher than group 1. In group 4, SOD activity was very high in comparison with groups 3 and 1, whereas MDA level was half that found in group 3. ATPase levels did not show a significant difference from those in group 2. Conclusions: These results demonstrate that amiloride is not effective in basilar arterial changes due to SAH. However, amiloride protects the side effects of Na~+ selenite. We suggest that this protection occurs by blocking the effect of Na~+ selenite on oxidation and on the Ca~(2+) influx mechanism.