Losartan enhances cognitive and structural neuroplasticity impairments in spontaneously hypertensive rats.

ABSTRACT

Hypertension is a risk factor for vascular dementia, which is the second most prevalent type of dementia, just behind Alzheimer's disease. This highlights the brain vulnerability due to hypertension, which may increase with aging. Thus, studying how hypertension affects neural cells and behavior, as well as the effects of antihypertensives on these alterations, it's important to understand the hypertension consequences in the brain. The spontaneously hypertensive rat (SHR) has been useful for the study of hypertension alterations in diverse organs, including the brain. Thus, we studied the losartan effects on cognitive and structural neuroplasticity impairments in SHR of 10 months of age. In the first instance, we evaluated the losartan effects on exploratory behavior and novel object recognition test (NORT) in the SHR. Then, we assessed the density and morphology of dendritic spines of pyramidal neurons from the prefrontal cortex (PFC) layers 3 and 5, and CA1 of the dorsal Hp (dHp). Our results indicate that in SHR, losartan treatment (2 months, 15 mg/Kg/day) reduces high blood pressure to age-matched vehicle-treated Wistar-Kyoto (WKY) rat levels. Moreover, losartan improved long-term memory in SHR compared with age-matched vehicle-treated WKY rats, without affecting the locomotor and anxiety behaviors. The behavioral improvement of the SHR can be associated with the increase in the number of dendritic spines and the mushroom spine population in the PFC and the dHp. In conclusion, losartan enhances cognitive impairments by controlling the high blood pressure and improving neuroplasticity in animals with chronic hypertension.