Abstract 073: Age-Dependent Hypertension-Related Cognitive Impairment And Neuroinflammation In Sprague Dawley Rats Can Be Reversed By An AT 1 R Antagonism

Abstract

Aim: We hypothesize paraventricular nucleus (PVN)-specific blood brain barrier (BBB) disruption and neuroinflammation increase hypertension and sympathoexcitation with age, promoting cognitive impairment, that can be attenuated by an Angiotensin II Type 1 Receptor (AT 1 R)-dependent mechanism in the aging Sprague Dawley (SD) rat. Methods: In male and female SD rats aged 3, 8 and 16 months old (MO) (N=6/gp) and 16 MO male rats treated with losartan (21 days; sc 3 mg/kg/day), blood pressure (BP; femoral artery cannulation), sympathetic tone to the vasculature (iv hexamethonium) and plasma NE (ELISA) was measured. Memory function was assessed by the novel object recognition task. BBB disruption was assessed via FITC extravasation and IHC/IF was performed for microglia (CD11b/c), astrocytes (GFAP), IL-6 and TNF-α in the PVN. Results: Aged male, but not female, SD rats develop HTN, sympathoexcitation, and cognitive impairment. PVN neuroinflammation, proinflammatory cytokine production and BBB disruption increased in male, but not female, rats with age. Losartan significantly lowered BP, reduced sympathoexcitation, attenuated BBB disruption and neuroinflammation, and reversed cognitive impairment in aged male rats. Conclusions: Our data suggest there is a potential protective role of female sex steroids in preventing the development of age-dependent HTN which is associated with PVN neuroinflammation. Concurrent with recent clinical findings, we found lowering blood pressure improved cognitive function and, thus, an AT 1 R antagonism represents a new therapeutic modality to improve cognitive performance in hypertensive individuals.