LOVASTATIN INCUBATION IMPROVES ACETYLCHOLINE-INDUCED RELAXATION IN ISOLATED AORTIC RINGS OF DIABETIC RAT

Abstract

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 -5 M) 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 N G –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.