PMID- 21292265
OWN - NLM
STAT- MEDLINE
DCOM- 20110809
LR  - 20131121
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 215
IP  - 2
DP  - 2011 Apr
TI  - Phytoestrogen alpha-zearalanol improves vascular function in ovariectomized 
      hyperhomocysteinemic rats.
PG  - 309-15
LID - 10.1016/j.atherosclerosis.2010.12.029 [doi]
AB  - Previous studies have showed that phytoestrogen alpha-zearalanol (alpha-ZAL) could 
      antagonize homocysteine (Hcy) induced endothelin-1 (ET-1) expression, oxidative 
      stress and apoptosis in human umbilical vein endothelial cells in vitro, however, 
      its effect on vascular function in vivo remains to be determined. This study was 
      designed to investigate the effects of alpha-ZAL on vascular function in 
      ovariectomized (OVX) hyperhomocysteinemia (HHcy) rats and explore the mechanisms 
      involved primarily. HHcy rat model was induced by diets containing 2.5% 
      methionine (Met) for 12 weeks. Forty adult female Wistar rats were assigned 
      randomly into five groups: (1) Con; (2) Met; (3) OVX+Met; (4) OVX+Met+alpha-ZAL; (5) 
      OVX+Met+17beta-E(2) (17beta-estradiol). Blood was collected to analyze plasma 
      estradiol, Hcy and ET-1. Thoracic aortas were isolated to detect its response to 
      phenylephrine (PE) and acetylcholine (ACh) or sodium nitroprusside (SNP). Aortas 
      eNOS expression was determined by Western blot. Thoracic aortas histological 
      characterization was analyzed by optical microscope and scanning electron 
      microscope (SEM). Rat plasma Hcy was significantly elevated after fed with 2.5% 
      methionine diets, and ovariectomy aggravated this elevation. Phytoestrogen alpha-ZAL 
      or 17beta-E(2) could attenuate this elevation. Plasma ET-1 levels increased 
      significantly in ovariectomized HHcy rats, and supplement with alpha-ZAL or 17beta-E(2) 
      could reverse these changes. In rats of OVX+Met group, PE elicited significantly 
      greater contraction in a dose-dependent manner in endothelium-intact thoracic 
      aortas rings; ACh elicited significantly less percentage relaxation. These 
      effects were significantly attenuated by supplement with alpha-ZAL or 17beta-E(2). There 
      was no significant difference between groups in relaxation induced by SNP whether 
      endothelium intact or not. Thoracic aortas morphology study also showed severe 
      endothelium injury in ovariectomized HHcy rats, both alpha-ZAL and 17beta-E(2) could 
      attenuate this change. Aortas eNOS expression was decreased in ovariectomized 
      HHcy rats, and supplement with alpha-ZAL or 17beta-E(2) could reverse these changes. 
      These findings demonstrated that alpha-ZAL could effectively alleviate the impairment 
      of endothelial cells and improve vascular function in ovariectomized HHcy rats by 
      decreasing plasma Hcy and antagonizing decreasing of aortas eNOS expression. This 
      protective effect is somewhat similar with 17beta-E(2).
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Zhen, Pan-pan
AU  - Zhen PP
AD  - Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical 
      University, You An Men Wai, Beijing 100069, PR China.
FAU - Duan, Jin-hong
AU  - Duan JH
FAU - Zhao, Qian
AU  - Zhao Q
FAU - Hou, Dan-dan
AU  - Hou DD
FAU - Wang, Hong-xia
AU  - Wang HX
FAU - Hong, Ni
AU  - Hong N
FAU - Zhen, Hui-xian
AU  - Zhen HX
FAU - Wang, Wen
AU  - Wang W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110119
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Endothelin-1)
RN  - 0 (Phytoestrogens)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 169D1260KM (Nitroprusside)
RN  - 1WS297W6MV (Phenylephrine)
RN  - 4TI98Z838E (Estradiol)
RN  - 76LO2L2V39 (Zeranol)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Aorta, Thoracic/drug effects/pathology/physiology
MH  - Endothelin-1/metabolism
MH  - Estradiol/pharmacology
MH  - Female
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/chemically induced/*physiopathology
MH  - Methionine
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Nitroprusside/pharmacology
MH  - Ovariectomy
MH  - Phenylephrine/pharmacology
MH  - Phytoestrogens/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Zeranol/*pharmacology
EDAT- 2011/02/05 06:00
MHDA- 2011/08/10 06:00
CRDT- 2011/02/05 06:00
PHST- 2010/06/28 00:00 [received]
PHST- 2010/12/23 00:00 [revised]
PHST- 2010/12/28 00:00 [accepted]
PHST- 2011/02/05 06:00 [entrez]
PHST- 2011/02/05 06:00 [pubmed]
PHST- 2011/08/10 06:00 [medline]
AID - S0021-9150(11)00047-5 [pii]
AID - 10.1016/j.atherosclerosis.2010.12.029 [doi]
PST - ppublish
SO  - Atherosclerosis. 2011 Apr;215(2):309-15. doi: 
      10.1016/j.atherosclerosis.2010.12.029. Epub 2011 Jan 19.