Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation.

Azza B. El-Remessy, Huda El Sayed Tawfik, Suraporn Matragoon, Bindu Pillai, Ruth B Caldwell, Robert William Caldwell

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.

Original languageEnglish (US)
Number of pages1
JournalExperimental Diabetes Research
Volume2010
StatePublished - Jan 1 2010

Fingerprint

rho-Associated Kinases
Peroxynitrous Acid
Lipid Peroxides
Vasodilation
Biological Availability
Acetylcholine
Blood Vessels
Diabetes
Activation
Coronary Vessels
Oxidative Stress
Phosphotransferases
Endothelial Cells
Glucose
Messenger RNA
Injections

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Peroxynitrite mediates diabetes-induced endothelial dysfunction : possible role of Rho kinase activation. / El-Remessy, Azza B.; Tawfik, Huda El Sayed; Matragoon, Suraporn; Pillai, Bindu; Caldwell, Ruth B; Caldwell, Robert William.

In: Experimental Diabetes Research, Vol. 2010, 01.01.2010.

Research output: Contribution to journalArticle

@article{8f540de3abec47269c55630a85da19e9,
title = "Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation.",
abstract = "Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50{\%} reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.",
author = "El-Remessy, {Azza B.} and Tawfik, {Huda El Sayed} and Suraporn Matragoon and Bindu Pillai and Caldwell, {Ruth B} and Caldwell, {Robert William}",
year = "2010",
month = "1",
day = "1",
language = "English (US)",
volume = "2010",
journal = "Experimental Diabesity Research",
issn = "1543-8600",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Peroxynitrite mediates diabetes-induced endothelial dysfunction

T2 - possible role of Rho kinase activation.

AU - El-Remessy, Azza B.

AU - Tawfik, Huda El Sayed

AU - Matragoon, Suraporn

AU - Pillai, Bindu

AU - Caldwell, Ruth B

AU - Caldwell, Robert William

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.

AB - Endothelial dysfunction is characterized by reduced bioavailability of NO due to its inactivation to form peroxynitrite or reduced expression of eNOS. Here, we examine the causal role of peroxynitrite in mediating diabetes-induced endothelial dysfunction. Diabetes was induced by STZ-injection, and rats received the peroxynitrite decomposition catalyst (FeTTPs, 15 mg/Kg/day) for 4 weeks. Vasorelaxation to acetylcholine, oxidative-stress markers, RhoA activity, and eNOS expression were determined. Diabetic coronary arteries showed significant reduction in ACh-mediated maximal relaxation compared to controls. Diabetic vessels showed also significant increases in lipid-peroxides, nitrotyrosine, and active RhoA and 50% reduction in eNOS mRNA expression. Treatment of diabetic animals with FeTTPS blocked these effects. Studies in aortic endothelial cells show that high glucose or peroxynitrite increases the active RhoA kinase levels and decreases eNOS expression and NO levels, which were reversed with blocking peroxynitrite or Rho kinase. Together, peroxynitrite can suppress eNOS expression via activation of RhoA and hence cause vascular dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=79952199787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952199787&partnerID=8YFLogxK

M3 - Article

C2 - 21052489

AN - SCOPUS:79952199787

VL - 2010

JO - Experimental Diabesity Research

JF - Experimental Diabesity Research

SN - 1543-8600

ER -