The
metabolic syndrome is closely related to dietary habits and seems to be associated with impairment of cognitive function in humans.
Angiotensin receptor blockers are widely used with the expectation of preventing cardiovascular events and
stroke and potential amelioration of the
metabolic syndrome. We examined the diet-induced changes of cognitive function in mice treated with a high-
salt and high-
cholesterol diet. C57BL/6J mice were fed a high-
salt (2% NaCl in
drinking water) and high-
cholesterol (1.25%
cholesterol, 10%
coconut oil) diet (HSCD) or a normal diet (ND), and subjected to 20 trials of a passive avoidance task every week from 8weeks of age. An age-dependent decline of the avoidance rate starting from 10weeks of age was observed in HSCD mice, whereas the avoidance rate gradually increased in the ND group.
Oral administration of an
angiotensin receptor blocker,
olmesartan, at a dose of 3mg/kg per day in
drinking water from 8weeks of age prevents this decline of avoidance rate in HSCD mice (49% vs. 82% at 12weeks of age). Treatment with
olmesartan significantly decreased serum
glucose and
cholesterol levels in HSCD mice, with a slight decrease in blood pressure. Administration of
olmesartan in HSCD-fed mice showed a 1.6-fold increase in
mRNA expression of a neuroprotective factor, MMS2, compared to HSCD-fed mice without
olmesartan.
Olmesartan attenuated the increase in
superoxide anion production detected by
dihydroethidium staining in the brain of HSCD mice. Our results suggest that
olmesartan could be therapeutically effective in preventing the impairment of quality of life in persons on a high-fat and high-
salt diet.