Dietary supplementation of the pyridoindole antioxidant stobadine reduces vascular impairment in streptozotocin-diabetic rats

We studied the influence of hyperglycemia lasting 1, 4, 6 and 8 months on t he reactivity and ultrastructure of the aorta in Wistar rats. Moreover, the effect of the pyridoindole antioxidant stobadine ((-)-cis-2,8-dimethyl-2,3 ,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole) on the changes induced by the 8-month hyperglycemia were studied. Hyperglycemia was induced by streptozot ocin (STZ, 55 mg/kg i.v.). In the functional study, responses to KCl, acety lcholine (ACh), noradrenaline (NA) and hydrogen peroxide were evaluated und er isometric conditions. The first changes in aortic reactivity started aft er I month of hyperglycemia and were exhibited by significantly increased N A-induced contractions. Relaxant responses to acetylcholine were decreased, although not significantly. Prolongation of hyperglycemia to 4, 6 and 8 mo nths did not cause any additional significant changes in responsiveness to NA. Decreased ACh-induced relaxation and increased contractile responses to H2O2 were observed in month 4. The functional responses were not substanti ally deteriorated by prolongation of hyperglycemia to 6 and 8 months. Ultra structural examination of the diabetic aorta showed disturbances in normal tissue organization. An 8-month supplementation of stobadine in diabetic ra ts resulted in the protection of aortic function as well as its ultrastruct ure. These results suggest that abnormalities occurring in the aorta of dia betic rats might result from the damaging effects of oxygen free radicals. (C) 2001 Prous Science. All rights reserved.