Abstract
Background: Independent of a high salt intake, Dahl Salt-Sensitive (DSS) rats demonstrate an age-associated increase in blood pressure (BP), and central arterial stiffness estimated by pulse wave velocity (PWV) accompanied by cognitive decline. We hypothesized, that anti-hypertensive treatment Lisinopril, in addition to BP decrease, will lower PWV and improve cognition of adult DSS. Methods: Twenty 6-mo old male DSS were kept on normal salt diet for the duration of the study; ten of them were continuously treated with Lisinopril (15 mg/kg/day) for 3 months. Systolic BP (SBP) and PWV (by doppler echocardiography) were measured, and open field test (OFT) was performed to assess locomotor and anxiety-like behavior at baseline prior to treatment and repeated in 3 months in 9-mo old rats. In a sub-cohort of DSS rats SBP was measured in 3-mo-old DSS. The data are presented as mean ± standard deviation and analyzed by 2-way ANOVA and T-test. Results: Prior to treatment, all DSS rats displayed hypertension and BP elevation with age (SBP: 170±11 vs. 142±5 mmHg, 6-mo vs. 3-mo; P<0.01). After 3 months, control untreated animals showed no difference in SBP and were hypertensive. Rats treated with Lisinopril for 3 months showed a decreased SBP (119±9 vs. 171±11 mmHg, P<0.0001) and a decreased PWV compared to their baseline prior to treatment (3.03±1.23 vs. 5.52±1.07 m/s p<0.05). In OFT, treatment with Lisinopril increased exploration of the center of the field compared to the control group (120±35 vs. 87±30% of distance traveled in center to baseline , p=0.05) without affecting total distance traveled, indicating a reduction in anxiety-like behavior. Conclusion: Lowering of BP and PWV is associated with reduced anxiety-like behavior in DSS, which indicate the connection of cardiovascular disorder and cognitive function in adult hypertensive DSS. Whether Lisinopril has an additional direct effect on brain structure and function in DSS rats will be further studied. This research was supported entirely by the Intramural research Program of the NIH, National institute on Aging
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