Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse

Hong Ding, Michael Hashem, William B. Wiehler, Winnie Lau, Jacqueline Martin, Julianne Reid, Christopher Triggle

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

1. Endothelial dysfunction plays a role in the development of atherosclerosis and diabetes-associated vascular disease and, in the streptozotocin (STZ)-induced apoE-deficient diabetic mouse, we report that, when compared to the citrate (CIT)-treated nondiabetic apoE-deficient control, acetylcholine (Ach)-mediated endothelium-dependent relaxation was reduced in the small mesenteric arteries (SMA) and the plaque-prone regions of the aorta from the STZ-diabetic mouse. 2. In the SMA the component of Ach-mediated relaxation that was attributed to nitric oxide (NO) from STZ-treated diabetic apoE-deficient mice was enhanced; however, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component was reduced. The EDHF component was assessed by determining the component of the Ach-mediated response that was resistant to the combination of the NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, indomethacin, and soluble guanylate cyclase inhibitor, ODQ, and inhibited by the combination of the intermediate conductance K Ca (IK Ca) inhibitor TRAM-34 and the small-conductance K Ca (SK Ca) inhibitor apamin. 3. Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P < 0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls. There was no difference in the IK Ca expression or in Cx 40, 43 and 45 mRNA levels between STZ- and CIT-treated mice. 4. The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression.

Original languageEnglish
Pages (from-to)1110-1118
Number of pages9
JournalBritish Journal of Pharmacology
Volume146
Issue number8
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

Fingerprint

Apolipoproteins E
Streptozocin
Mesenteric Arteries
Endothelium
Citric Acid
Acetylcholine
Nitric Oxide Synthase
Apamin
Messenger RNA
Connexin 43
Cyclooxygenase Inhibitors
Microvessels
Vascular Diseases
Indomethacin
Aorta
Atherosclerosis
Nitric Oxide

Keywords

  • Apamin
  • apoE-deficient
  • Atherosclerosis
  • Connexins
  • Diabetes
  • EDHF
  • Endothelium
  • eNOS
  • SK channels
  • Streptozotocin
  • TRAM-34

ASJC Scopus subject areas

  • Pharmacology

Cite this

Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse. / Ding, Hong; Hashem, Michael; Wiehler, William B.; Lau, Winnie; Martin, Jacqueline; Reid, Julianne; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 146, No. 8, 12.2005, p. 1110-1118.

Research output: Contribution to journalArticle

Ding, Hong ; Hashem, Michael ; Wiehler, William B. ; Lau, Winnie ; Martin, Jacqueline ; Reid, Julianne ; Triggle, Christopher. / Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse. In: British Journal of Pharmacology. 2005 ; Vol. 146, No. 8. pp. 1110-1118.
@article{088816594b284f00906b2990e4cee352,
title = "Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse",
abstract = "1. Endothelial dysfunction plays a role in the development of atherosclerosis and diabetes-associated vascular disease and, in the streptozotocin (STZ)-induced apoE-deficient diabetic mouse, we report that, when compared to the citrate (CIT)-treated nondiabetic apoE-deficient control, acetylcholine (Ach)-mediated endothelium-dependent relaxation was reduced in the small mesenteric arteries (SMA) and the plaque-prone regions of the aorta from the STZ-diabetic mouse. 2. In the SMA the component of Ach-mediated relaxation that was attributed to nitric oxide (NO) from STZ-treated diabetic apoE-deficient mice was enhanced; however, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component was reduced. The EDHF component was assessed by determining the component of the Ach-mediated response that was resistant to the combination of the NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, indomethacin, and soluble guanylate cyclase inhibitor, ODQ, and inhibited by the combination of the intermediate conductance K Ca (IK Ca) inhibitor TRAM-34 and the small-conductance K Ca (SK Ca) inhibitor apamin. 3. Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P < 0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls. There was no difference in the IK Ca expression or in Cx 40, 43 and 45 mRNA levels between STZ- and CIT-treated mice. 4. The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression.",
keywords = "Apamin, apoE-deficient, Atherosclerosis, Connexins, Diabetes, EDHF, Endothelium, eNOS, SK channels, Streptozotocin, TRAM-34",
author = "Hong Ding and Michael Hashem and Wiehler, {William B.} and Winnie Lau and Jacqueline Martin and Julianne Reid and Christopher Triggle",
year = "2005",
month = "12",
doi = "10.1038/sj.bjp.0706417",
language = "English",
volume = "146",
pages = "1110--1118",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse

AU - Ding, Hong

AU - Hashem, Michael

AU - Wiehler, William B.

AU - Lau, Winnie

AU - Martin, Jacqueline

AU - Reid, Julianne

AU - Triggle, Christopher

PY - 2005/12

Y1 - 2005/12

N2 - 1. Endothelial dysfunction plays a role in the development of atherosclerosis and diabetes-associated vascular disease and, in the streptozotocin (STZ)-induced apoE-deficient diabetic mouse, we report that, when compared to the citrate (CIT)-treated nondiabetic apoE-deficient control, acetylcholine (Ach)-mediated endothelium-dependent relaxation was reduced in the small mesenteric arteries (SMA) and the plaque-prone regions of the aorta from the STZ-diabetic mouse. 2. In the SMA the component of Ach-mediated relaxation that was attributed to nitric oxide (NO) from STZ-treated diabetic apoE-deficient mice was enhanced; however, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component was reduced. The EDHF component was assessed by determining the component of the Ach-mediated response that was resistant to the combination of the NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, indomethacin, and soluble guanylate cyclase inhibitor, ODQ, and inhibited by the combination of the intermediate conductance K Ca (IK Ca) inhibitor TRAM-34 and the small-conductance K Ca (SK Ca) inhibitor apamin. 3. Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P < 0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls. There was no difference in the IK Ca expression or in Cx 40, 43 and 45 mRNA levels between STZ- and CIT-treated mice. 4. The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression.

AB - 1. Endothelial dysfunction plays a role in the development of atherosclerosis and diabetes-associated vascular disease and, in the streptozotocin (STZ)-induced apoE-deficient diabetic mouse, we report that, when compared to the citrate (CIT)-treated nondiabetic apoE-deficient control, acetylcholine (Ach)-mediated endothelium-dependent relaxation was reduced in the small mesenteric arteries (SMA) and the plaque-prone regions of the aorta from the STZ-diabetic mouse. 2. In the SMA the component of Ach-mediated relaxation that was attributed to nitric oxide (NO) from STZ-treated diabetic apoE-deficient mice was enhanced; however, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component was reduced. The EDHF component was assessed by determining the component of the Ach-mediated response that was resistant to the combination of the NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, indomethacin, and soluble guanylate cyclase inhibitor, ODQ, and inhibited by the combination of the intermediate conductance K Ca (IK Ca) inhibitor TRAM-34 and the small-conductance K Ca (SK Ca) inhibitor apamin. 3. Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P < 0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls. There was no difference in the IK Ca expression or in Cx 40, 43 and 45 mRNA levels between STZ- and CIT-treated mice. 4. The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression.

KW - Apamin

KW - apoE-deficient

KW - Atherosclerosis

KW - Connexins

KW - Diabetes

KW - EDHF

KW - Endothelium

KW - eNOS

KW - SK channels

KW - Streptozotocin

KW - TRAM-34

UR - http://www.scopus.com/inward/record.url?scp=28944444040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28944444040&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0706417

DO - 10.1038/sj.bjp.0706417

M3 - Article

C2 - 16231005

AN - SCOPUS:28944444040

VL - 146

SP - 1110

EP - 1118

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 8

ER -