Abstract 222: Impairment of Autonomic Function and Increased Aldosterone in Metabolic Syndrome Model Rats Mediates Circadian Blood Pressure Rhythms

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Abstract

[Aim] Metabolic syndrome (MetS) is significantly associated with abnormal blood pressure (BP) circadian rhythms, although the underlying mechanism(s) is unclear. Using SHR/NDmcr-cp (SHRcp), manifesting with hypertension, obesity, insulin resistance and dyslipidemia, we examined the mechanisms underlying abnormal circadian rhythms of BP in MetS.

[Methods] (1)We surgically implanted telemetry devices in control SHR and SHRcp to monitor BP continuously. We performed a cross-spectral analysis, using a fast Fourier transformation algorithm, of arterial pulse waves to determine autonomic function and baroreceptor reflex function. Urine samples in dark (active) phase and light (inactive) phase were collected with metabolic cages to measure factors associated with blood pressure control.

(2)SHRcp were orally administered azilsartan (1mg/kg/day), an AT1 receptor blocker, once daily at the beginning of the active phase, to examine the effects of azilsartan on the above mentioned parameters.

[Results] (1)SHRcp exhibited non-dipper type hypertension, although SHR exhibited dipper-type hypertension. Compared with SHR, SHRcp showed an increased low frequency (LF) power of sBP and a decreased spontaneous baroreceptor reflex gain (sBRG). Thus, SHRcp was characterized by enhanced vascular sympathetic tone and impaired baroreflex function 24 hrs a day. Urine norepinephrine(NE) and aldosterone excretion levels were greater in SHRcp over 24 hrs than in SHR.

(2)Azilsartan treatment once daily normalized BP in SHRcp over 24 hrs. Azilsartan had a greater hypotensive effect in SHRcp than in SHR, thus indicating the key role of hypertension in SHRcp. Azilsartan decreased LF of sBP, increased sBRG, and reduced urinary NE excretion levels in SHRcp. Azilsartan also reduced urinary aldosterone excretion over 24 hrs and serum aldosterone concentration, thus increasing urinary sodium excretion in SHRcp.

[Conclusion] SHRcp, a model of MetS,exhibit non-dipper type hypertension, and thus they are suitable models for studying abnormal BP circadian rhythms. The mechanism of abnormal BP circadian rhythm in SHRcp was attributed to an impaired autonomic nervous system and aldosterone-induced sodium retention, which were both mediated by AT1 receptor.

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