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Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke
被引:22
作者:
Coucha, Maha
[1
]
Li, Weiguo
[1
,4
]
Johnson, Maribeth H.
[2
]
Fagan, Susan C.
[3
,4
,5
]
Ergul, Adviye
[1
,4
]
机构:
[1] Georgia Regents Univ, Dept Physiol, Augusta, GA 30912 USA
[2] Georgia Regents Univ, Dept Biostat, Augusta, GA 30912 USA
[3] Georgia Regents Univ, Dept Neurol, Augusta, GA 30912 USA
[4] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA USA
[5] Univ Georgia, Coll Pharm, Program Clin & Expt Therapeut, Augusta, GA USA
来源:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
|
2013年
/
305卷
/
12期
基金:
美国国家卫生研究院;
关键词:
contralateral hemisphere;
ischemia-reperfusion injury;
myogenic tone;
nitration;
peroxynitrite;
PEROXYNITRITE DECOMPOSITION CATALYSTS;
SIGNALING MECHANISMS;
THRESHOLD DURATION;
NITRIC-OXIDE;
BLOOD-FLOW;
RECEPTOR;
ENDOTHELIUM;
EPICATECHIN;
ANTAGONISM;
REACTIVITY;
D O I:
10.1152/ajpheart.00535.2013
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after stroke. Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl) prophyrinato iron (III), or the nitration inhibitor epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo oxygen-glucose deprivation with and without glycoprotein 91 tat (NADPH oxidase inhibitor) or N-omega-nitro-L-arginine methyl ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the sham group (P < 0.001). Vessels exposed to ex vivo oxygen-glucose deprivation experienced a similar loss of myogenic tone. Inhibition of peroxynitrite parent radicals significantly improved the myogenic tone. Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P < 0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly increased in both hemispheres versus the sham group and was normalized with epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that sham operation rather than the nonischemic side should be used as a control in preclinical stroke studies.
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页码:H1726 / H1735
页数:10
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