Effects of Donepezil on Nonlinear Arterial Pressure and Pulse Interval Dynamics in Spontaneously Hypertensive Rats (SHR)

Objectives: This study aimed to evaluate the effects of donepezil, an anticholinesterase agent that potentiates parasympathetic function, in the nonlinear dynamics of blood pressure (BP) and pulse interval (PI) from spontaneously hypertensive rats (SHR). Entropy-based approaches which quantify the irregularity or unpredictability of time series were employed. Additionally, detrended fluctuation analysis (DFA) was applied to estimate the degree of self-similarity in the time series. We hypothesized that donepezil improves both entropy and DFA indices of BP and PI. Methods: Male SHR or Wistar-Kyoto (WKY) rats (5 weeks old) were implanted with subcutaneous osmotic mini-pumps for donepezil (DON) administration (1.4 mg/kg/day) or vehicle. At the end of the treatment (16 weeks), conscious WKY (N=12) and SHR treated with donepezil (N=8), or vehicle (N=9), had their BP directly recorded during 1h. Time series (15 min) from systolic BP and PI were generated and used to calculate sample (SampEn), fuzzy (FuzzyEn), and dispersion (DispEn) entropy, as well as DFA scale exponents in short (α1; 5≤n≤15), mid (α2; 20≤n≤100) and long (α3; 100≤n≤500) windows. The results are shown as mean ± SD. One-Way ANOVA, followed by Tukey’s post-test, evaluated differences between the WKY, SHR, and SHR+DON groups. Results: The data are displayed in the table. Lower PI DispEn was observed in SHR treated with DON compared to WKY. Entropy values of BP series were found smaller in SHR and SHR+DON compared to WKY rats. For DFA of the PI series, SHR+DON showed higher α1 compared to the WKY. Moreover, SHR displayed higher α3 when compared to the WKY. In the series of BP values, the results showed higher α2 and α3 in SHR compared to WKY. [Formula: see text] Conclusion: These findings showed that SHR exhibited lower BP entropy and higher DFA of BP and IP compared with WKY. However, donepezil did not prevent these changes of non-linear indices from BP and PI variability in SHR. Funding Sources: FAPESP, Process 2020/06043-7. CNPq, Process 306994/2021-6 and 423999/2021-4. FAEPA. CAPES. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.