title: Novel mechanism for disrupted circadian blood pressure rhythm in a rat model of metabolic syndrome--the critical role of angiotensin II.
abstract: BACKGROUND
  This study was performed to determine the characteristics and mechanism of hypertension in SHR/NDmcr-cp(+/+) rats (SHRcp), a new model of metabolic syndrome, with a focus on the autonomic nervous system, aldosterone, and angiotensin II.
  
  
  RESULTS
  We measured arterial blood pressure (BP) in SHRcp by radiotelemetry combined with spectral analysis using a fast Fourier transformation algorithm and examined the effect of azilsartan, an AT1 receptor blocker. Compared with control Wistar-Kyoto rats (WKY) and SHR, SHRcp exhibited a nondipper-type hypertension and displayed increased urinary norepinephrine excretion and increased urinary and plasma aldosterone levels. Compared with WKY and SHR, SHRcp were characterized by an increase in the low-frequency power (LF) of systolic BP and a decrease in spontaneous baroreflex gain (sBRG), indicating autonomic dysfunction. Thus, SHRcp are regarded as a useful model of human hypertension with metabolic syndrome. Oral administration of azilsartan once daily persistently lowered BP during the light period (inactive phase) and the dark period (active phase) in SHRcp more than in WKY and SHR. Thus, angiotensin II seems to be involved in the mechanism of disrupted diurnal BP rhythm in SHRcp. Azilsartan significantly reduced urinary norepinephrine and aldosterone excretion and significantly increased urinary sodium excretion in SHRcp. Furthermore, azilsartan significantly reduced LF of systolic BP and significantly increased sBRG in SHRcp.
  
  
  CONCLUSIONS
  These results strongly suggest that impairment of autonomic function and increased aldosterone in SHRcp mediate the effect of angiotensin II on circadian blood pressure rhythms.
authors: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors: Daisuke
authors: D
authors: Sueta
authors: Keiichiro
authors: K
authors: Kataoka
authors: Nobutaka
authors: N
authors: Koibuchi
authors: Kensuke
authors: K
authors: Toyama
authors: Ken
authors: K
authors: Uekawa
authors: Tetsuji
authors: T
authors: Katayama
authors: Ma
authors: M
authors: Mingjie
authors: Takashi
authors: T
authors: Nakagawa
authors: Hidefumi
authors: H
authors: Waki
authors: Masanobu
authors: M
authors: Maeda
authors: Osamu
authors: O
authors: Yasuda
authors: Kunihiko
authors: K
authors: Matsui
authors: Hisao
authors: H
authors: Ogawa
authors: Shokei
authors: S
authors: Kim-Mitsuyama
mesh_terms: D000450:Aldosterone / Q000502:physiology; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000804:Angiotensin II; D000450:Aldosterone
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