title: Blood pressure variability, impaired autonomic function and vascular senescence in aged spontaneously hypertensive rats are ameliorated by angiotensin blockade.
abstract: OBJECTIVE
  Elderly hypertensive patients are characterized by blood pressure (BP) variability, impaired autonomic function, and vascular endothelial dysfunction and stiffness. However, the mechanisms causing these conditions are unclear. The present study examined the effect of angiotensin receptor blockers (ARBs) on aged spontaneously hypertensive rats (SHR).
  
  
  METHODS
  We surgically implanted telemetry devices in SHR and WKY at the age of 15 weeks (Young) and 80 weeks (Aged). Aged SHR were orally administered either olmesartan or valsartan once daily at 19:00 h (at the beginning of the dark period (active phase)) for 4 weeks to examine the effects on BP variability, impaired autonomic function, and vascular senescence.
  
  
  RESULTS
  Aging and hypertension in SHR additively caused the following: increased low frequency (LF) power of systolic BP, a decreased spontaneous baroreceptor reflex gain (sBRG), increased BP variability, increased urinary norepinephrine excretion, increased vascular senescence-related beta-galactosidase positive cells and oxidative stress. Treatment with olmesartan or valsartan significantly ameliorated these changes in aged SHR. However, olmesartan ameliorated these changes in aged SHR better than valsartan. The reductions in BP caused by olmesartan in aged SHR were sustained longer than reductions by valsartan. This result indicates longer-lasting inhibition of the AT1 receptor by olmesartan than by valsartan.
  
  
  CONCLUSIONS
  ARBs ameliorated autonomic dysfunction, BP variability, and vascular senescence in aged SHR. Olmesartan ameliorated the aging-related disorders better than valsartan and was associated with longer-lasting AT1 receptor inhibition by olmesartan. Thus, the magnitude of improvement of these aging-related abnormalities differs for ARBs.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sueta
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Toyama
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Uekawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: MingJie
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Physiology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Waki
authors.affiliation: Department of Physiology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860-8556, Japan. Electronic address: mitsuyam@gpo.kumamoto-u.ac.jp.
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D000375:Aging / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000737:chemistry; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009206:Myocardium / Q000473:pathology; D019255:NADPH Oxidases / Q000032:analysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012021:Reflex, Abnormal / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; D000068756:Valsartan; C437965:olmesartan; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D001616:beta-Galactosidase; D014633:Valine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
keywords: Angiotensin; Blood pressure variability; Circadian blood pressure; Oxidative stress; Vascular senescence