The effects of the pre-treatment of intravenous nimodipine on Na+-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat

Excessive calcium influx has been implicated in the pathophysiology of isch emic cerebral damage. The effects of nimodipine, a calcium antagonist on th e Na+-K+/MG(+2) ATPase activity, Ca+2/Mg+2 ATPase, lipid peroxidation, and early ultrastructural findings were examined at the acute stage of ischemia in the rat brain. Ischemia was produced by permanent unilateral occlusion of the middle cerebral artery. In Group I; the rats which had no ischemia a nd not received medication were used for determining Na+ -K+/Mg+2 ATPase, C a+2/Mg+2 ATPase, the extent of lipid peroxidation by measuring the malondia ldehyde content and normal ultrastructural findings. In Group II, the rats which had only subtemporal craniectomy without occlusion and received salin e solution were used for determining the effect of the surgical procedure o n the biochemical indices and ultrastructural findings. ln Group iii, the r ats received saline solution following the occlusion in the same amount of nimodipine and in the same duration as used in Group IV. In Group IV, nimod ipine pre-treatment 15 min before occlusion (mug kg(-1) min(-1) over a 10 m in period) was applied i.v. Na+-K+/Mg+2 ATPase and Ca+2/Mg+2 ATPase activit ies decreased significantly and promptly as early as 70min and remained at a lower level than the contralateral hemisphere in the same group and at th e normal level in Group 1. Nimodipine pre-treatment immediately attenuated the inactivation of Na+ -K+/ Mg+2 ATPase (p < 0.05) but there was no change on Ca+2/Mg+2 ATPase activity (p < 0.051. Malondialdehyde content increased significantly in Group III following ischemia as early as 30 min. Nimodipi ne pre-treatment decreased the malondialdehyde level in Group IV (p < 0.05) . This study supports the possibility that nimodipine pre-treatment effects the membrane stabilizing properties via inhibiting the lipid peroxidation and subsequently restoring some membrane bound and lipid dependent enzymes' activity such as Na+-K+/Mg+2 ATPase and the ultrastructural findings.