PMID- 22471901
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20211203
IS  - 1525-6006 (Electronic)
IS  - 1064-1963 (Linking)
VI  - 34
IP  - 6
DP  - 2012
TI  - Combination therapy of olmesartan and azelnidipine inhibits sympathetic activity 
      associated with reducing oxidative stress in the brain of hypertensive rats.
PG  - 456-62
LID - 10.3109/10641963.2012.666603 [doi]
AB  - It has been demonstrated that the antihypertensive drugs with the antioxidant 
      action on the brainstem inhibit the sympathetic activity and consequently 
      decrease blood pressure and heart rate (HR) in hypertensive rats. Combination 
      drugs of the angiotensin receptor blocker and calcium channel blocker, such as 
      olmesartan (OLM)/azelnidipine (AZ) and candesartan (CAN)/amlodipine (AM), are 
      widely used for treating hypertension in Japan. In this study, it was 
      investigated whether there are differences in the antioxidant effect in the brain 
      and the sympathoinhibitory effect between OLM/AZ and CAN/AM combination therapies 
      in stroke-prone spontaneously hypertensive rats (SHRSP). OLM/AZ (10/8 mg kg(-1) 
      day(-1)), CAN/AM (4/2.5 mg kg(-1) day(-1)), or vehicle was orally administered 
      for 30 days to SHRSP. OLM/AZ and CAN/AM markedly decreased systolic blood 
      pressure to the same extent. OLM/AZ decreased HR to a greater extent than CAN/AM. 
      Urinary norepinephrine excretion as a marker of sympathetic activity was 
      unchanged in the CAN/AM group, but reduced in the OLM/AZ group. Oxidative stress 
      in the whole brain assessed using the in vivo electron spin resonance method was 
      similarly decreased in both OLM/AZ and CAN/AM groups. Importantly, thiobarbituric 
      acid reactive substance levels in the brainstem were significantly lower in the 
      OLM/AZ group, but not in the CAN/AM group, than in the vehicle group. These 
      results suggest that combination therapy of either OLM/AZ or CAN/AM does not 
      induce reflex-mediated sympathetic activation despite the marked blood pressure 
      reduction, which is associated with an antioxidant effect in the brain regions 
      affecting the sympathetic activity. Furthermore, the antioxidant effect in the 
      brainstem and the sympathoinhibitory effect of OLM/AZ combination may be greater 
      than those of CAN/AM combination treatment.
FAU - Shinohara, Keisuke
AU  - Shinohara K
AD  - Department of Cardiovascular Medicine, Kyushu University Graduate School of 
      Medical Sciences, Fukuoka, Japan.
FAU - Hirooka, Yoshitaka
AU  - Hirooka Y
FAU - Ogawa, Kiyohiro
AU  - Ogawa K
FAU - Kishi, Takuya
AU  - Kishi T
FAU - Yasukawa, Keiji
AU  - Yasukawa K
FAU - Utsumi, Hideo
AU  - Utsumi H
FAU - Sunagawa, Kenji
AU  - Sunagawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120403
PL  - England
TA  - Clin Exp Hypertens
JT  - Clinical and experimental hypertension (New York, N.Y. : 1993)
JID - 9305929
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Dihydropyridines)
RN  - 0 (Imidazoles)
RN  - 0 (Tetrazoles)
RN  - 5GZ3E0L9ZU (Azetidinecarboxylic Acid)
RN  - 6M97XTV3HD (Olmesartan Medoxomil)
RN  - PV23P19YUG (azelnidipine)
RN  - S8Q36MD2XX (candesartan)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*therapeutic use
MH  - Azetidinecarboxylic Acid/*analogs & derivatives/therapeutic use
MH  - Benzimidazoles/therapeutic use
MH  - Biphenyl Compounds
MH  - Blood Pressure/*drug effects
MH  - Brain/drug effects
MH  - Calcium Channel Blockers/*therapeutic use
MH  - Dihydropyridines/*therapeutic use
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Hypertension/*drug therapy
MH  - Imidazoles/*therapeutic use
MH  - Male
MH  - Olmesartan Medoxomil
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Tetrazoles/*therapeutic use
EDAT- 2012/04/05 06:00
MHDA- 2013/03/30 06:00
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
AID - 10.3109/10641963.2012.666603 [doi]
PST - ppublish
SO  - Clin Exp Hypertens. 2012;34(6):456-62. doi: 10.3109/10641963.2012.666603. Epub 
      2012 Apr 3.