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.