Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats

Ayako Makino, K. Kamata

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aim: To examine the mechanisms underlying the elevated plasma endothelin-1 (ET-1) in diabetes and its vascular effects. Results: Relationships between the plasma ET-1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10-week streptozotocin (STZ)-induced diabetic rats. In contrast, at 1 week after the STZ injection only plasma ET-1 and glucose levels were elevated, suggesting that the hyperglycaemia might trigger the excess production of ET-1. Incubation with high glucose promoted the release of ET-1 from the isolated mesenteric arterial bed. In STZ-induced diabetic rats, the maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasoconstriction and vasodilation induced by the ETB-receptor agonist IRL-1620 in this bed were significantly impaired. The vascular responses induced by these ET receptor agonists were restored to normal by chronic treatment of diabetic rats with insulin for 7 or 4 weeks. Conclusions: These results suggest: (1) that the marked increase in plasma glucose in STZ-induced diabetic rats elevates the plasma ET-1; and (2) that the decreased contractile and vasodilator responses of the mesenteric arterial bed to ET-1 receptor agonists may be due to desensitization of not only ETA, but also ETB receptors, an effect secondary to the elevation of plasma ET-1.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume2
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Endothelin-1
Streptozocin
Glucose
Blood Vessels
Endothelin-2
Endothelin A Receptors
Vasoconstriction
Vasodilator Agents
Vasodilation
Hyperglycemia
Triglycerides
Cholesterol
Insulin
Injections

Keywords

  • Diabetes
  • Endothelin-1
  • Endothelium
  • ET receptor
  • ET receptor
  • Glucose
  • Mesenteric arterial bed
  • Rat
  • Streptozotocin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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abstract = "Aim: To examine the mechanisms underlying the elevated plasma endothelin-1 (ET-1) in diabetes and its vascular effects. Results: Relationships between the plasma ET-1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10-week streptozotocin (STZ)-induced diabetic rats. In contrast, at 1 week after the STZ injection only plasma ET-1 and glucose levels were elevated, suggesting that the hyperglycaemia might trigger the excess production of ET-1. Incubation with high glucose promoted the release of ET-1 from the isolated mesenteric arterial bed. In STZ-induced diabetic rats, the maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasoconstriction and vasodilation induced by the ETB-receptor agonist IRL-1620 in this bed were significantly impaired. The vascular responses induced by these ET receptor agonists were restored to normal by chronic treatment of diabetic rats with insulin for 7 or 4 weeks. Conclusions: These results suggest: (1) that the marked increase in plasma glucose in STZ-induced diabetic rats elevates the plasma ET-1; and (2) that the decreased contractile and vasodilator responses of the mesenteric arterial bed to ET-1 receptor agonists may be due to desensitization of not only ETA, but also ETB receptors, an effect secondary to the elevation of plasma ET-1.",
keywords = "Diabetes, Endothelin-1, Endothelium, ET receptor, ET receptor, Glucose, Mesenteric arterial bed, Rat, Streptozotocin",
author = "Ayako Makino and K. Kamata",
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AU - Kamata, K.

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N2 - Aim: To examine the mechanisms underlying the elevated plasma endothelin-1 (ET-1) in diabetes and its vascular effects. Results: Relationships between the plasma ET-1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10-week streptozotocin (STZ)-induced diabetic rats. In contrast, at 1 week after the STZ injection only plasma ET-1 and glucose levels were elevated, suggesting that the hyperglycaemia might trigger the excess production of ET-1. Incubation with high glucose promoted the release of ET-1 from the isolated mesenteric arterial bed. In STZ-induced diabetic rats, the maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasoconstriction and vasodilation induced by the ETB-receptor agonist IRL-1620 in this bed were significantly impaired. The vascular responses induced by these ET receptor agonists were restored to normal by chronic treatment of diabetic rats with insulin for 7 or 4 weeks. Conclusions: These results suggest: (1) that the marked increase in plasma glucose in STZ-induced diabetic rats elevates the plasma ET-1; and (2) that the decreased contractile and vasodilator responses of the mesenteric arterial bed to ET-1 receptor agonists may be due to desensitization of not only ETA, but also ETB receptors, an effect secondary to the elevation of plasma ET-1.

AB - Aim: To examine the mechanisms underlying the elevated plasma endothelin-1 (ET-1) in diabetes and its vascular effects. Results: Relationships between the plasma ET-1 level and the levels of other plasma constituents (glucose, cholesterol, and triglyceride) were found in 10-week streptozotocin (STZ)-induced diabetic rats. In contrast, at 1 week after the STZ injection only plasma ET-1 and glucose levels were elevated, suggesting that the hyperglycaemia might trigger the excess production of ET-1. Incubation with high glucose promoted the release of ET-1 from the isolated mesenteric arterial bed. In STZ-induced diabetic rats, the maximum contractile response of the mesenteric arterial bed to ET-1 was significantly reduced, and the vasoconstriction and vasodilation induced by the ETB-receptor agonist IRL-1620 in this bed were significantly impaired. The vascular responses induced by these ET receptor agonists were restored to normal by chronic treatment of diabetic rats with insulin for 7 or 4 weeks. Conclusions: These results suggest: (1) that the marked increase in plasma glucose in STZ-induced diabetic rats elevates the plasma ET-1; and (2) that the decreased contractile and vasodilator responses of the mesenteric arterial bed to ET-1 receptor agonists may be due to desensitization of not only ETA, but also ETB receptors, an effect secondary to the elevation of plasma ET-1.

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KW - Streptozotocin

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