PMID- 24839960
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20181202
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 92
IP  - 10
DP  - 2014 Oct
TI  - Synergistic neuroprotective effects of combined treatment with olmesartan plus 
      azelnidipine in stroke-prone spontaneously hypertensive rats.
PG  - 1330-7
LID - 10.1002/jnr.23406 [doi]
AB  - An angiotensin 2 type 1 receptor blocker, olmesartan, and a calcium channel 
      blocker, azelnidipine, possess not only an antihypertensive effect but also an 
      antioxidative effect and other beneficial effects. In the present study, we 
      examined the efficacy of olmesartan and azelnidipine monotherapy (2 mg/kg or 10 
      mg/kg each) and their combination therapy (1 mg/kg each) on stroke-prone 
      spontaneously hypertensive rats (SHR-SP) in relation to oxidative stress, 
      inflammation, and the neurovascular unit. In comparison with the vehicle group, 
      body weight, regional cerebral blood flow, and motor function were preserved, 
      whereas systolic blood pressure and diastolic blood pressure decreased in the 
      five drug-treatment groups. Spontaneous infarct volume decreased with the 
      low-dose combination of olmesartan plus azelnidipine and with the high-dose 
      olmesartan, with a further decrease in the high-dose azelnidipine group. In 
      addition, these drugs dose-dependently reduced oxidative stresses, 
      proinflammatory molecules, and well-preserved components of the neurovascular 
      unit. The low-dose combination of olmesartan plus azelnidipine showed a better 
      effect than the low-dose olmesartan or azelnidipine monotherapy. The present 
      study shows that the low-dose combination of olmesartan plus azelnidipine 
      demonstrates a greater synergistic benefit than monotherapy with a low-dose of 
      olmesartan or azelnidipine in SHR-SP for preventing spontaneous infarct volume, 
      reducing oxidative stresses and proinflammatory molecules, and imparting 
      neurovascular protection. In addition, a high-dose of olmesartan showed a greater 
      benefit without the lowering of blood pressure, probably because of the 
      antioxidative and anti-inflammatory effects. A high dose of azelnidipine showed 
      the best benefit, probably because of the two effects mentioned above related to 
      the lowering of blood pressure.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Omote, Yoshio
AU  - Omote Y
AD  - Department of Neurology, Graduate School of Medicine, Dentistry, and 
      Pharmaceutical Sciences, Okayama University, Shikatacho, Okayama, Japan.
FAU - Deguchi, Kentaro
AU  - Deguchi K
FAU - Kono, Syoichiro
AU  - Kono S
FAU - Liu, Wentao
AU  - Liu W
FAU - Kurata, Tomoko
AU  - Kurata T
FAU - Hishikawa, Nozomi
AU  - Hishikawa N
FAU - Yamashita, Toru
AU  - Yamashita T
FAU - Ikeda, Yoshio
AU  - Ikeda Y
FAU - Abe, Koji
AU  - Abe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140520
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type IV)
RN  - 0 (Dihydropyridines)
RN  - 0 (Imidazoles)
RN  - 0 (Tetrazoles)
RN  - 5GZ3E0L9ZU (Azetidinecarboxylic Acid)
RN  - 8W1IQP3U10 (olmesartan)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - PV23P19YUG (azelnidipine)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Azetidinecarboxylic Acid/*analogs & derivatives/therapeutic use
MH  - Blood Pressure/drug effects
MH  - Brain Injuries/diagnosis/etiology/pathology/*prevention & control
MH  - Chemokine CCL2/metabolism
MH  - Collagen Type IV/metabolism
MH  - Dihydropyridines/*therapeutic use
MH  - Disease Models, Animal
MH  - Drug Synergism
MH  - Drug Therapy, Combination
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Heart Rate/drug effects
MH  - Imidazoles/*therapeutic use
MH  - Laser-Doppler Flowmetry
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Motor Activity/drug effects
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Stroke/*drug therapy/genetics
MH  - Tetrazoles/*therapeutic use
OTO - NOTNLM
OT  - SHR-SP
OT  - azelnidipine
OT  - neurovascular unit
OT  - olmesartan
OT  - oxidative stress
EDAT- 2014/05/21 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/05/21 06:00
PHST- 2014/02/08 00:00 [received]
PHST- 2014/03/29 00:00 [revised]
PHST- 2014/04/02 00:00 [accepted]
PHST- 2014/05/21 06:00 [entrez]
PHST- 2014/05/21 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - 10.1002/jnr.23406 [doi]
PST - ppublish
SO  - J Neurosci Res. 2014 Oct;92(10):1330-7. doi: 10.1002/jnr.23406. Epub 2014 May 20.