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) |
|---|---|
| Pages (from-to) | 47-55 |
| Number of pages | 9 |
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2000 |
| Externally published | Yes |
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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
Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats. / Makino, Ayako; Kamata, K.
In: Diabetes, Obesity and Metabolism, Vol. 2, No. 1, 2000, p. 47-55.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats
AU - Makino, Ayako
AU - Kamata, K.
PY - 2000
Y1 - 2000
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.
KW - Diabetes
KW - Endothelin-1
KW - Endothelium
KW - ET receptor
KW - ET receptor
KW - Glucose
KW - Mesenteric arterial bed
KW - Rat
KW - Streptozotocin
UR - http://www.scopus.com/inward/record.url?scp=0034522451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034522451&partnerID=8YFLogxK
U2 - 10.1046/j.1463-1326.2000.00024.x
DO - 10.1046/j.1463-1326.2000.00024.x
M3 - Article
VL - 2
SP - 47
EP - 55
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 1
ER -