Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke

Maha Coucha, Weiguo Li, Maribeth H Johnson, Susan C. Fagan, Adviye Ergul

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16 Citations (Scopus)

Abstract

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 Nω-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number12
DOIs
StatePublished - Dec 15 2013

Fingerprint

Peroxynitrous Acid
Middle Cerebral Artery
Reperfusion Injury
Stroke
Reperfusion
Catechin
Cerebrovascular Circulation
Proteins
Oxygen
Glucose
NADPH Oxidase
Middle Cerebral Artery Infarction
Vascular Resistance
Wistar Rats
Glycoproteins
Oxidative Stress
Ischemia
Iron
Perfusion
Pressure

Keywords

  • Contralateral hemisphere
  • Ischemia-reperfusion injury
  • Myogenic tone
  • Nitration
  • Peroxynitrite

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke",
abstract = "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 Nω-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.",
keywords = "Contralateral hemisphere, Ischemia-reperfusion injury, Myogenic tone, Nitration, Peroxynitrite",
author = "Maha Coucha and Weiguo Li and Johnson, {Maribeth H} and Fagan, {Susan C.} and Adviye Ergul",
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T1 - Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke

AU - Coucha, Maha

AU - Li, Weiguo

AU - Johnson, Maribeth H

AU - Fagan, Susan C.

AU - Ergul, Adviye

PY - 2013/12/15

Y1 - 2013/12/15

N2 - 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 Nω-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.

AB - 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 Nω-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.

KW - Contralateral hemisphere

KW - Ischemia-reperfusion injury

KW - Myogenic tone

KW - Nitration

KW - Peroxynitrite

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U2 - 10.1152/ajpheart.00535.2013

DO - 10.1152/ajpheart.00535.2013

M3 - Article

VL - 305

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

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