Acetylcholine-induced vasodilation in the perfused kidney of the streptozotocin-induced diabetic rat: role of prostacyclin.

Using the perfused kidneys of age-matched controls and streptozotocin (STZ)-induced diabetic rats, we previously demonstrated that endothelial dysfunction is present in STZ-induced diabetic rats and that acetylcholine (ACh) increases the level of 6-keto-prostaglandin F(1 alpha) (a metabolite of prostacyclin) in the effluent from such perfused kidneys. Here, we investigated whether the ACh-induced relaxation in the perfused kidney is modulated by prostacyclin and/or thromboxane A(2) (TXA(2)) in the STZ-induced diabetic state. ACh-induced renal vasodilatation was significantly weaker in STZ-induced diabetic rats than in age-matched controls, and it was not affected by treatment with 10 microM furegrelate (TXA(2) -synthase inhibitor) or 1 microM SQ29548 (TXA(2) -receptor antagonist) in either group. However, it was attenuated by 10 microM tranylcypromine (prostacyclin-synthesis inhibitor), but only in the diabetic group. These results suggest that the endothelium-dependent relaxation induced by ACh in the renal vascular bed of STZ-induced diabetic rats is regulated by prostacyclin, not by TXA(2). Increased prostacyclin-signaling may occur to help compensate for the impaired endothelial function seen in the kidney in long-term diabetic states.