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 the 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 streptozotocin (STZ, 55 mg/kg i.v.). In the functional study, responses to KCl, acetylcholine (ACh), noradrenaline (NA) and hydrogen peroxide were evaluated under isometric conditions. The first changes in aortic reactivity started after 1 month of hyperglycemia and were exhibited by significantly increased NA-induced contractions. Relaxant responses to acetylcholine were decreased, although not significantly. Prolongation of hyperglycemia to 4, 6 and 8 months 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 substantially deteriorated by prolongation of hyperglycemia to 6 and 8 months. Ultrastructural examination of the diabetic aorta showed disturbances in normal tissue organization. An 8-month supplementation of stobadine in diabetic rats resulted in the protection of aortic function as well as its ultrastructure. These results suggest that abnormalities occurring in the aorta of diabetic rats might result from the damaging effects of oxygen free radicals.