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Effects of eplerenone on cerebral aldosterone levels and brain lesions in spontaneously hypertensive rats

ABSTRACT Evidence indicates that renin-angiotensin-aldosterone system (RAS) inhibitors can protect the brain in Alzheimer’s disease and Parkinson’s disease. The current study evaluated the relationship between aldosterone and tissue damage in the brains of spontaneously hypertensive rats (SHRs) and whether the RAS inhibitor eplerenone can mitigate the damage seen in these rats. SHRs were randomly divided into eplerenone (n = 10) and SHR (n = 10) groups, and Wistar-Kyoto (WKY) rats (n = 10) were used as controls. Eplerenone 50 mg/kg/day was administered orally to the eplerenone group. Pathological changes to the hippocampal formation, plasma and encephalic aldosterone, and plasma potassium levels were compared among the groups. After 10 weeks, rats in the eplerenone and SHR groups showed higher systolic BP (p = .01) than the control group. Aldosterone levels in the brain were higher in the SHR group (0.20 ± 0.06 pg/ml) than in the eplerenone (0.14 ± 0.05 pg/ml, p = .044) or control (0.12 ± 0.07 pg/ml, p = .007) groups. Plasma aldosterone levels in the SHR group were 1.7 times higher than those in the control group (p = .006). Cerebral cortex was thinner in the SHR group (225.18 ± 15.43 μm) than in the eplerenone (240.38 ± 12.85 μm, p < .01) or control (244.72 ± 18.92 μm, p < .01) groups. Thickness did not differ between the latter two groups. The SHR group exhibited apoptotic cells in the hippocampal formation, which were rare in the eplerenone and control groups. Plasma potassium levels were higher in the eplerenone group than those in the other two groups (p < .05). Our results showed that eplerenone can alleviate brain damage (thinning of cortex and increased apoptosis) caused by aldosterone in a rat model of hypertension.