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

Summary 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 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.