lovastatin incubation improves acetylcholine-induced relaxation in isolated aortic rings of diabetic rat

to evaluate the acute effect of lovastatin on diabetic endothelial dysfunction, we examined this effect on the aortic rings of streptozotocin-diabetic rats. the endothelial function was assessed in aortic rings isolated from diabetic rats, 12 weeks after treatment with streptozotocin (45 mg/kg, i.p.). the concentration-response curve to acetylcholine (ach) in the aortic rings precontracted with phenylephrine (10-6 m) was significantly diminished in diabetic groups; and maximum relaxation in control and diabetic groups were 82±1.93% and 48±2.39% respectively (a 42% decrease, p<0.001). incubation with lovastatin (10-5m) for 10 min, significantly improved the ach-induced relaxation of diabetic groups and the maximum relaxation increased to 74.2 ±3.3% (a 54% increase, p<0.001). incubation with ng –nitro-l-arginine methyl ester hydrochloride (l-name; 5x10-7 m) for 20 min eliminated a significant difference in ach – induced relaxation responses in diabetic and control groups and also eliminated the improving effect of lovastatin in diabetic groups. on the other hand 10 min incubation with indomethacin (10-5 m) did not eliminate the difference in ach-induced relaxation responses in diabetic and control groups and also did not eliminate the improving effect of lovastatin in diabetic groups. lovastatin did not modify sodium nitroprosside-induced relaxation in either diabetic or control groups and also did not induce any direct relaxation. therefore, it is concluded that incubation of aortic rings with lovastatin significantly improves endothelium-dependent relaxation in diabetic groups by increasing the nitric oxide bioavailability, most probably due to its’ antioxidant effects.