Time-course changes in plasma endothelin-1 and its effects on the mesenteric arterial bed in streptozotocin-induced diabetic rats.
OBJECTIVE
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 ET(B)-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 ET(A), but also ET(B) receptors, an effect secondary to the elevation of plasma ET-1.
Makino
A
A
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Kamata
K
K
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D019332:Endothelin-1 / Q000097:blood* / Q000494:pharmacology / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D014665:Vasodilator Agents; C074308:sovateltide; D013311:Streptozocin