Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes

Mostafa M. Elgebaly, Vera Portik-Dobos, Kamakshi Sachidanandam, David Rychly, Daniel Malcom, Maribeth H Johnson, Adviye Ergul

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ETA receptors mediates oxidative stress whereas ETB receptors display opposing effects. Plasma total antioxidant status (TAS) and 8-isoprostane (8-iso PGF) as well as total nitrotyrosine levels in mesenteric resistance vessels were measured in control Wistar and diabetic Goto-Kakizaki (GK) rats (n = 5-10) treated with vehicle, ETA antagonist (atrasentan, 5 mg/kg/day), or ETB receptor antagonist (A-192621, 15 or 30 mg/kg/day, low and high dose, respectively) for 4 weeks. 8-iso PGF (pg/ml) levels were significantly higher in low dose A-192621 treatment groups of control and diabetic rats than in atrasentan or high-dose A-192621 treated groups. Protein nitration was increased in diabetes and ETA receptor antagonism prevented this increase. TAS levels were similar in all experimental groups. Thus, ET-1 contributes to oxidative stress in type 2 diabetes and ET receptor antagonism with atrasentan or A-192612 displays differential effects depending on dose and receptor subtype.

Original languageEnglish (US)
Pages (from-to)125-130
Number of pages6
JournalVascular Pharmacology
Volume47
Issue number2-3
DOIs
StatePublished - Aug 1 2007

Fingerprint

A 192621
Type 2 Diabetes Mellitus
Oxidative Stress
8-epi-prostaglandin F2alpha
Dinoprost
Antioxidants
Endothelin-1
Control Groups
atrasentan
Proteins

Keywords

  • Endothelin
  • Oxidative stress
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Elgebaly, M. M., Portik-Dobos, V., Sachidanandam, K., Rychly, D., Malcom, D., Johnson, M. H., & Ergul, A. (2007). Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes. Vascular Pharmacology, 47(2-3), 125-130. https://doi.org/10.1016/j.vph.2007.05.006

Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes. / Elgebaly, Mostafa M.; Portik-Dobos, Vera; Sachidanandam, Kamakshi; Rychly, David; Malcom, Daniel; Johnson, Maribeth H; Ergul, Adviye.

In: Vascular Pharmacology, Vol. 47, No. 2-3, 01.08.2007, p. 125-130.

Research output: Contribution to journalArticle

Elgebaly, MM, Portik-Dobos, V, Sachidanandam, K, Rychly, D, Malcom, D, Johnson, MH & Ergul, A 2007, 'Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes', Vascular Pharmacology, vol. 47, no. 2-3, pp. 125-130. https://doi.org/10.1016/j.vph.2007.05.006
Elgebaly, Mostafa M. ; Portik-Dobos, Vera ; Sachidanandam, Kamakshi ; Rychly, David ; Malcom, Daniel ; Johnson, Maribeth H ; Ergul, Adviye. / Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes. In: Vascular Pharmacology. 2007 ; Vol. 47, No. 2-3. pp. 125-130.
@article{455676ee27d04cbc97b998ab28f342aa,
title = "Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes",
abstract = "Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ETA receptors mediates oxidative stress whereas ETB receptors display opposing effects. Plasma total antioxidant status (TAS) and 8-isoprostane (8-iso PGF2α) as well as total nitrotyrosine levels in mesenteric resistance vessels were measured in control Wistar and diabetic Goto-Kakizaki (GK) rats (n = 5-10) treated with vehicle, ETA antagonist (atrasentan, 5 mg/kg/day), or ETB receptor antagonist (A-192621, 15 or 30 mg/kg/day, low and high dose, respectively) for 4 weeks. 8-iso PGF2α (pg/ml) levels were significantly higher in low dose A-192621 treatment groups of control and diabetic rats than in atrasentan or high-dose A-192621 treated groups. Protein nitration was increased in diabetes and ETA receptor antagonism prevented this increase. TAS levels were similar in all experimental groups. Thus, ET-1 contributes to oxidative stress in type 2 diabetes and ET receptor antagonism with atrasentan or A-192612 displays differential effects depending on dose and receptor subtype.",
keywords = "Endothelin, Oxidative stress, Type 2 diabetes",
author = "Elgebaly, {Mostafa M.} and Vera Portik-Dobos and Kamakshi Sachidanandam and David Rychly and Daniel Malcom and Johnson, {Maribeth H} and Adviye Ergul",
year = "2007",
month = "8",
day = "1",
doi = "10.1016/j.vph.2007.05.006",
language = "English (US)",
volume = "47",
pages = "125--130",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier Inc.",
number = "2-3",

}

TY - JOUR

T1 - Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes

AU - Elgebaly, Mostafa M.

AU - Portik-Dobos, Vera

AU - Sachidanandam, Kamakshi

AU - Rychly, David

AU - Malcom, Daniel

AU - Johnson, Maribeth H

AU - Ergul, Adviye

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ETA receptors mediates oxidative stress whereas ETB receptors display opposing effects. Plasma total antioxidant status (TAS) and 8-isoprostane (8-iso PGF2α) as well as total nitrotyrosine levels in mesenteric resistance vessels were measured in control Wistar and diabetic Goto-Kakizaki (GK) rats (n = 5-10) treated with vehicle, ETA antagonist (atrasentan, 5 mg/kg/day), or ETB receptor antagonist (A-192621, 15 or 30 mg/kg/day, low and high dose, respectively) for 4 weeks. 8-iso PGF2α (pg/ml) levels were significantly higher in low dose A-192621 treatment groups of control and diabetic rats than in atrasentan or high-dose A-192621 treated groups. Protein nitration was increased in diabetes and ETA receptor antagonism prevented this increase. TAS levels were similar in all experimental groups. Thus, ET-1 contributes to oxidative stress in type 2 diabetes and ET receptor antagonism with atrasentan or A-192612 displays differential effects depending on dose and receptor subtype.

AB - Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ETA receptors mediates oxidative stress whereas ETB receptors display opposing effects. Plasma total antioxidant status (TAS) and 8-isoprostane (8-iso PGF2α) as well as total nitrotyrosine levels in mesenteric resistance vessels were measured in control Wistar and diabetic Goto-Kakizaki (GK) rats (n = 5-10) treated with vehicle, ETA antagonist (atrasentan, 5 mg/kg/day), or ETB receptor antagonist (A-192621, 15 or 30 mg/kg/day, low and high dose, respectively) for 4 weeks. 8-iso PGF2α (pg/ml) levels were significantly higher in low dose A-192621 treatment groups of control and diabetic rats than in atrasentan or high-dose A-192621 treated groups. Protein nitration was increased in diabetes and ETA receptor antagonism prevented this increase. TAS levels were similar in all experimental groups. Thus, ET-1 contributes to oxidative stress in type 2 diabetes and ET receptor antagonism with atrasentan or A-192612 displays differential effects depending on dose and receptor subtype.

KW - Endothelin

KW - Oxidative stress

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=34447639753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447639753&partnerID=8YFLogxK

U2 - 10.1016/j.vph.2007.05.006

DO - 10.1016/j.vph.2007.05.006

M3 - Article

VL - 47

SP - 125

EP - 130

JO - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

IS - 2-3

ER -