Superoxide dismutase gene expression and activity in the brain of spontaneously hypertensive rats and normotensive rats

Objective To determine if changes in superoxide dismutase ( SOD) in the bra in occur in the hypertensive state, Methods We compared the levels of the two main subtypes of this enzyme in s pontaneously hypertensive rats (SHR) with age-matched normotensive Wistar K yoto (WKY) rats using enzyme activity estimation, Western blotting for enzy me contents, and Northern blotting of mRNA level. Five discrete brain regio ns, cerebrocortex, hypothalamus, hippocampus, the remaining non-cortex cere brum (NCC area), and cerebellum, were employed for comparison in 30 - 31 we eks old rats. Results A lower level of both Mn-SOD activity and Mn-SOD mRNA expression wa s found in all areas of the brain of SHR as compared with WKY rats. Also, t he mRNA levels of Cu, Zn-SOD in the brain of SHR differed from WKY rats in parallel to the enzyme activities. The activity and mRNA expression of Cu, Zn-SOD were lower in the hypothalamus and cerebellum of SHR but the mRNA le vel and the activity in hippocampus were significantly higher in the SHR co mpared to WKY rats. No differences for Cu, Zn-SOD were observed in cerebroc ortex or NCC area in the two species. However, the amount of SOD enzyme sub types, determined by Western blotting analysis, was not different between S HR and WKY rats. Conclusions The results indicate a lower gene expression and less activity of Mn-SOD in SHR brain. This alternation of SOD may be one of the important factors for the vulnerability of the brain from oxygen free radicals or ma y be related to the pathogenesis of hypertension in this species.