Regional Distribution of Superoxide Dismutase in the Brain and Myocardium of the Stroke‐prone Spontaneously Hypertensive Rat

Abstract

1. Enzyme activities and contents of manganese and copperzinc superoxide dismutase (Mn-, Cu/Zn-SOD) and oxygen free-radical scavengers were determined in the myocardium (right, left ventricle) and brain (cerebral cortex, hippocampus) of 15 and 31 week old stroke-prone spontaneously hypertensive rats (SHRSP).2. In 15 week old SHRSP myocardium, both Mn-and Cu/Zn-SOD activities were higher but in 31 week old SHRSP, these were lower than that in Wistar-Kyoto (WKY) rats. Further, correlation between Mn-SOD content and activity in 31 week old SHRSP myocardium showed that specific activity was lower than that in WKY.3. In 15 and 31 week old SHRSP cerebral cortex and hippocampus, SOD content and activity showed a tendency to be lower than that in WKY.4. These results indicate that enzymatically inactive or lowactive Mn-SOD protein exists in SHRSP myocardium, and that the alteration of SOD may be one of the causative factors for the vulnerability of the myocardium and brain against 02-radicals.

Increased Levels of Superoxide in Brains from Old Female Rats

“…Neither the effect of age nor hypertension on SOD levels have been investigated previously in female animals. However, Kimoto et al [8] found that both MnSOD and Cu/Zn SOD levels tended to be lower in male SHRSP than WKY cerebral cortex and hippocampus and to decrease significantly between 15 and 31 weeks of age in SHRSP. Although in our study neither Mn SOD nor Cu/Zn SOD levels were decreased in hippocampus or stratum of the old animals the importance of SOD in regulating O z2 2 levels was demonstrated by the large increase in O z2 2 levels observed in the presence of the Cu/Zn SOD inhibitor DETC in cortical tissue from young WKY and SHRSP.…”

“…[14,16] Brains from SHRSP have been reported to exhibit enhanced lipid peroxidation [17] and lower SOD levels. [8] The aim of the present study was therefore to examine levels of O z2 2 in brains of young and old WKY and SHRSP and to determine the role of SOD's and E 2 in regulating O z2 2 levels.…”

“…[7] Decreased levels of SOD have been suggested to be one of the causative factors for vulnerability of myocardium and brain against O z2 2 radicals in spontaneously hypertensive stroke prone rats (SHRSP). [8] As well as dismutation to hydrogen peroxide O z2 2 levels may also be reduced by direct scavenging by antioxidants. Low molecular weight antioxidants such as a-tocopherol, ascorbate and selenium have been shown to be effective in many animal studies.…”

The Inflammatory Aspect of the Microcirculation in Hypertension: Oxidative Stress, Leukocytes/Endothelial Interaction, Apoptosis

“…A further contribution to the enhanced oxidative stress in hypertensive individuals can be attributed to the suppression of scavenger mechanisms for ROS. In the SHR, mRNA levels, and enzyme activity of SOD and catalase are reduced in most but not all tissues (20,62,70,71,169,185,189). Treatment with SOD or analogues serves in part to control blood pressure (104,132).…”

Failure of Probucol to Prolong Survival in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats.

“…As another exacerbating factor, oxidative stress has been implicated in SHRSP. Lipid peroxidation in the brain and myocardial tissues is higher in SHRSP than in WKY (10,26). Longterm treatment with tannins, which have a potent radical scavenging action, has been shown to suppress the incidence of stroke and prolong the life span of SHRSP without lowering blood pressure (11).…”