Elevated plasma endothelin-1 level in streptozotocin-induced diabetic rats and responsiveness of the mesenteric arterial bed to endothelin-1

Ayako Makino, Katsuo Kamata

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72 Citations (Scopus)

Abstract

1. Both the plasma endothelin-1 (ET-1) levels and the plasma glucose levels were markedly elevated in streptozotocin (STZ)-induced diabetic rats. 2. The maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasodilatation induced by the ET(B)-receptor agonist IRL-1620 in the mesenteric arterial bed was significantly reduced in STZ-induced diabetic rats. 3. ET-1 (10-8 M) caused a transient vasodilatation followed by a marked vasoconstriction in methoxamine-preconstricted mesenteric arterial beds. The ET-1-induced vasodilatation was significantly larger in beds from diabetic rats than in those from age-matched controls. By contrast, the ET-1-induced vasoconstriction was significantly smaller in STZ-induced diabetic rats than in the controls. 4. Both removal of the endothelium with Triton X-100 and preincubation with BQ-788 (10-6 M) (ET(B)-receptor antagonist) abolished the ET-1-induced vasodilatation. Preincubation with BQ-485 (10-6 M) or BQ-123 (3 x 10-6) (ET(A)-receptor antagonist) significantly augmented the ET-1-induced vasodilatation in control mesenteric arterial beds, but not that in beds from diabetic rats. 5. These results demonstrate that marked increases not only in plasma glucose, but also in plasma ET-1 occur in STZ-induced diabetic rats. We suggest that the decreased contractile response and the increased vasodilator response of the mesenteric arterial bed to ET-1 may both be due to desensitization of ET(A) receptors, though ET(B) receptors may also be desensitized. This desensitization may result from the elevation of the plasma ET-1 levels seen in STZ-induced diabetic rats.

Original languageEnglish (US)
Pages (from-to)1065-1072
Number of pages8
JournalBritish Journal of Pharmacology
Volume123
Issue number6
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Endothelin-1
Streptozocin
Vasodilation
Vasoconstriction
Methoxamine
Glucose
Octoxynol
Vasodilator Agents
Endothelium

Keywords

  • Diabetes
  • Endothelin-1
  • Endothelium
  • ET(A) receptor
  • ET(B) receptor
  • Mesenteric arterial bed

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Elevated plasma endothelin-1 level in streptozotocin-induced diabetic rats and responsiveness of the mesenteric arterial bed to endothelin-1",
abstract = "1. Both the plasma endothelin-1 (ET-1) levels and the plasma glucose levels were markedly elevated in streptozotocin (STZ)-induced diabetic rats. 2. The maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasodilatation induced by the ET(B)-receptor agonist IRL-1620 in the mesenteric arterial bed was significantly reduced in STZ-induced diabetic rats. 3. ET-1 (10-8 M) caused a transient vasodilatation followed by a marked vasoconstriction in methoxamine-preconstricted mesenteric arterial beds. The ET-1-induced vasodilatation was significantly larger in beds from diabetic rats than in those from age-matched controls. By contrast, the ET-1-induced vasoconstriction was significantly smaller in STZ-induced diabetic rats than in the controls. 4. Both removal of the endothelium with Triton X-100 and preincubation with BQ-788 (10-6 M) (ET(B)-receptor antagonist) abolished the ET-1-induced vasodilatation. Preincubation with BQ-485 (10-6 M) or BQ-123 (3 x 10-6) (ET(A)-receptor antagonist) significantly augmented the ET-1-induced vasodilatation in control mesenteric arterial beds, but not that in beds from diabetic rats. 5. These results demonstrate that marked increases not only in plasma glucose, but also in plasma ET-1 occur in STZ-induced diabetic rats. We suggest that the decreased contractile response and the increased vasodilator response of the mesenteric arterial bed to ET-1 may both be due to desensitization of ET(A) receptors, though ET(B) receptors may also be desensitized. This desensitization may result from the elevation of the plasma ET-1 levels seen in STZ-induced diabetic rats.",
keywords = "Diabetes, Endothelin-1, Endothelium, ET(A) receptor, ET(B) receptor, Mesenteric arterial bed",
author = "Ayako Makino and Katsuo Kamata",
year = "1998",
doi = "10.1038/sj.bjp.0701704",
language = "English (US)",
volume = "123",
pages = "1065--1072",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
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TY - JOUR

T1 - Elevated plasma endothelin-1 level in streptozotocin-induced diabetic rats and responsiveness of the mesenteric arterial bed to endothelin-1

AU - Makino, Ayako

AU - Kamata, Katsuo

PY - 1998

Y1 - 1998

N2 - 1. Both the plasma endothelin-1 (ET-1) levels and the plasma glucose levels were markedly elevated in streptozotocin (STZ)-induced diabetic rats. 2. The maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasodilatation induced by the ET(B)-receptor agonist IRL-1620 in the mesenteric arterial bed was significantly reduced in STZ-induced diabetic rats. 3. ET-1 (10-8 M) caused a transient vasodilatation followed by a marked vasoconstriction in methoxamine-preconstricted mesenteric arterial beds. The ET-1-induced vasodilatation was significantly larger in beds from diabetic rats than in those from age-matched controls. By contrast, the ET-1-induced vasoconstriction was significantly smaller in STZ-induced diabetic rats than in the controls. 4. Both removal of the endothelium with Triton X-100 and preincubation with BQ-788 (10-6 M) (ET(B)-receptor antagonist) abolished the ET-1-induced vasodilatation. Preincubation with BQ-485 (10-6 M) or BQ-123 (3 x 10-6) (ET(A)-receptor antagonist) significantly augmented the ET-1-induced vasodilatation in control mesenteric arterial beds, but not that in beds from diabetic rats. 5. These results demonstrate that marked increases not only in plasma glucose, but also in plasma ET-1 occur in STZ-induced diabetic rats. We suggest that the decreased contractile response and the increased vasodilator response of the mesenteric arterial bed to ET-1 may both be due to desensitization of ET(A) receptors, though ET(B) receptors may also be desensitized. This desensitization may result from the elevation of the plasma ET-1 levels seen in STZ-induced diabetic rats.

AB - 1. Both the plasma endothelin-1 (ET-1) levels and the plasma glucose levels were markedly elevated in streptozotocin (STZ)-induced diabetic rats. 2. The maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasodilatation induced by the ET(B)-receptor agonist IRL-1620 in the mesenteric arterial bed was significantly reduced in STZ-induced diabetic rats. 3. ET-1 (10-8 M) caused a transient vasodilatation followed by a marked vasoconstriction in methoxamine-preconstricted mesenteric arterial beds. The ET-1-induced vasodilatation was significantly larger in beds from diabetic rats than in those from age-matched controls. By contrast, the ET-1-induced vasoconstriction was significantly smaller in STZ-induced diabetic rats than in the controls. 4. Both removal of the endothelium with Triton X-100 and preincubation with BQ-788 (10-6 M) (ET(B)-receptor antagonist) abolished the ET-1-induced vasodilatation. Preincubation with BQ-485 (10-6 M) or BQ-123 (3 x 10-6) (ET(A)-receptor antagonist) significantly augmented the ET-1-induced vasodilatation in control mesenteric arterial beds, but not that in beds from diabetic rats. 5. These results demonstrate that marked increases not only in plasma glucose, but also in plasma ET-1 occur in STZ-induced diabetic rats. We suggest that the decreased contractile response and the increased vasodilator response of the mesenteric arterial bed to ET-1 may both be due to desensitization of ET(A) receptors, though ET(B) receptors may also be desensitized. This desensitization may result from the elevation of the plasma ET-1 levels seen in STZ-induced diabetic rats.

KW - Diabetes

KW - Endothelin-1

KW - Endothelium

KW - ET(A) receptor

KW - ET(B) receptor

KW - Mesenteric arterial bed

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