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 language | English (US) |
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Pages (from-to) | 47-55 |
Number of pages | 9 |
Journal | Diabetes, Obesity and Metabolism |
Volume | 2 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2000 |
Externally published | Yes |
Keywords
- Diabetes
- Endothelin-1
- Endothelium
- Glucose
- Mesenteric arterial bed
- Rat
- Streptozotocin
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology