Effect of Anti‐hypertensive Treatment Lisinopril on Anxiety‐like Behavior in Adult Hypertensive Dahl Salt‐Sensitive Rats

Abstract

BackgroundIndependent of a high salt intake, Dahl Salt‐Sensitive (DSS) rats demonstrate an age‐associated increase in blood pressure (BP) accompanied by cognitive decline. We sought to explore the effect of anti‐hypertensive treatment, Lisinopril, which lowers tissue angiotensin II levels, on BP and behavior in adult DSS rats. We hypothesized, that Lisinopril, in addition to BP decrease, will affect the cognitive status of adult DSS.MethodsSixteen 6‐month‐old male DSS rats were kept on normal salt diet for the duration of the study; eight of them were continuously treated with 250 mg/L Lisinopril administered through their water for 2 months (15 mg/kg/day), and eight DSS rats remained on regular water as a control. Systolic BP (SBP) was measured in conscious male DSS rats via tail‐cuff plethysmography, and open field test (OFT) was performed to assess locomotor and anxiety‐like behavior at baseline prior to treatment and repeated 2 months after treatment began. Statistical regression analyses were performed using Prizm 7: 1‐way and 2‐way ANOVA, T‐test when applicable. The data are presented as mean ± standard deviation.ResultsPrior to treatment, all DSS rats displayed hypertension and BP elevation with age (SBP: 170 ± 11 vs. 142 ± 5 mmHg, 6‐mo vs. 3‐mo, n=16; P<0.01). After 2 months, control untreated animals showed no difference in SBP and were hypertensive (170 ± 15 vs. 168 ± 13 mmHg, 8‐mo vs. 6‐mo, n=8; n/s). Rats treated with Lisinopril for 2 months showed a dramatically decreased SBP compared to their baseline prior to treatment (119 ± 9 vs. 171 ± 11 mmHg, P<0.0001, n=8; Fig. 1), verifying the efficacy of the drug. In OFT, treatment with Lisinopril increased exploration of the center of the field compared to the control group (160 ± 45 vs. 91 ± 55 % of distance traveled in center to baseline, p=0.0166, n=8/group; Fig. 2) without affecting total distance traveled, indicating a reduction in anxiety‐like behavior. Furthermore, there was a significant negative correlation between SBP and increased activity in the center of the field (Pearson R=−0.58, R2=0.34, P=0.018; Fig. 3), suggesting anxiolytic effects of BP lowering medication.ConclusionLowering of BP 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 functions in DSS rats will be further studied.Support or Funding InformationSupported by NIH/NIA Intramural Research ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.