Effect of Sacubitril/Valsartan, Ivabradine, and Captopril on Anxiety-like Behavior in Spontaneously Hypertensive Rats

Cardiovascular disorders and the medications used to treat them can affect physiological patterns of behavior. The aim of the present study was to determine whether the dual inhibition of neprilysin and angiotensin II-sacubitril/valsartan (ARNI) can modify anxiety-like behavior in male spontaneously hypertensive rats (SHR). We compared ARNI with two other drugs in the portfolio of heart failure treatment, captopril and ivabradine. Six groups (n = 13) of 12-week-old rats were treated for six weeks: control (Wistar rats), control + ARNI, SHR, SHR + ARNI, SHR + captopril, and SHR + ivabradine. The elevated plus maze test, the open field test, and the light-dark box test were used to determine anxiety-like behavior. SHRs exhibited higher systolic blood pressure (SBP), heart rate (HR), left ventricular weight (LVW), and hydroxyproline concentration (LVHP) but displayed a reduced level of anxiety-like behavior in comparison to controls. ARNI reduced SBP, HR, and LVW but had no significant effect on the level of anxiety in SHR, and similar results were achieved by captopril and ivabradine. Additionally, correlation analysis indicated that anxiety-like behavior in Wistar rats or SHR, either with or without cardiovascular therapy, was independent of SBP, HR, LVW, or LVHP. The level of anxiety-like behavior can, therefore, be considered part of the inherent neurobehavioral traits unrelated to fundamental hemodynamic or structural cardiovascular parameters.