Memory impairment in spontaneously hypertensive rats is associated with hippocampal hypoperfusion and hippocampal vascular dysfunction

Abstract

We investigated the effect of chronic hypertension on hippocampal arterioles (HippAs) and hippocampal perfusion as underlying mechanisms of memory impairment, and how large artery stiffness relates to HippA remodeling. Using male spontaneously hypertensive rats (SHR) and normotensive Wistar rats ( n = 12/group), long-term (LTM) and spatial memory were tested using object recognition and spontaneous alternation tasks. Hippocampal blood flow was measured via hydrogen clearance basally and during hypercapnia. Reactivity of isolated and pressurized HippAs to pressure and pharmacological activators and inhibitors was investigated. To determine large artery stiffness, distensibility and elastin content were measured in thoracic aorta. SHR had impaired LTM and spatial memory associated with decreased basal blood flow (68 ± 12 mL/100 g/min) vs. Wistar (111 ± 28 mL/100 g/min, p < 0.01) that increased during hypercapnia similarly between groups. Compared to Wistar, HippAs from SHR had increased tone at 60 mmHg (58 ± 9% vs. 37 ± 7%, p < 0.01), and decreased reactivity to small- and intermediate-conductance calcium-activated potassium (SK/IK) channel activation. HippAs in both groups were unaffected by NOS inhibition. Decreased elastin content correlated with increased stiffness in aorta of SHR that was associated with increased stiffness and hypertrophic remodeling of HippAs. Hippocampal vascular dysfunction during hypertension could potentiate memory deficits and may provide a therapeutic target to limit vascular cognitive impairment.