Abstract 13940: Using an Angiotensin Converting Enzyme Inhibitor to Treat Cardiovascular and Cognitive Decline in a Rat Model of Vascular Dementia

Abstract

Background: Aged Dahl salt sensitive rats (DSS) rats represent a model of vascular dementia, i.e., they develop central arterial stiffness (CAS), hypertension, and cognitive decline. DSS rats have compromised renin-angiotensin system (RAS) which is activated with age and contributes to hypertension. This study examined whether angiotensin converting enzyme (ACE) inhibitor, lisinopril, affects CAS and cognitive functions in aged male DSS (n=26). Methods & Results: Following initial measurements at 16-mo of age (baseline; BL), DSS were administered lisinopril through their water (LISI; 15mg/kg/day, n=11) or control treatment (n=15) for 2-mo. Pulse wave velocity (PWV), a marker of CAS, and systolic blood pressure (SBP) were measured at BL and at 18-mo of age. Open field test (OFT) to assess anxiety-like behavior and Morris water maze (MWM) to assess spatial memory were performed at 18-mo, then aortae and hearts were collected and weighed. Aortic wall collagen abundance was estimated by histochemistry. Statistical analyses were performed by 2-way ANOVA mixed effects model and t-test. The data are presented as mean ± SEM. At 18-mo of age, control animals had high SBP similar to BL (187±4 vs. 184±7 mmHg), while LISI-treated DSS had lower SBP by 39±4 mmHg vs. BL (p<0.01). PWV in control rats increased from 16 to 18-mo (7.0±0.6 vs. 10.8±1.0 m/s; p<0.05), while PWV in LISI-treated DSS decreased after 2-mo of treatment (7.1±0.3 vs. 5.4±0.3 m/s; p<0.01). Lower heart weights (2.9±0.1 vs. 3.7±0.3 g/kg BW; p<0.01), aortic weights (4.4±0.1 vs. 5.0±0.2 mg/mm/kg BW; p<0.01), and aortic medial collagen abundance (14.0±0.3 vs. 19.6±1.0 % of total; p<0.01) were observed in the LISI-treated rats vs. control rats. No differences between LISI-treated and control groups at 18-mo (38±10 vs. 25±6 cm traveled in center) were found in OFT. MWM results indicated that neither group at 18-mo of age was able to learn the task and therefore could not be accurately assessed for differences in spatial memory. Conclusion: Initiation of anti-hypertensive treatment in old age was effective in reducing aortic fibrosis and lowering SBP and PWV in DSS rats. Longer treatment may be needed to improve cognitive function in this model of vascular dementia. Supported by the NIH/NIA Intramural Research Program