Simvastatin, Atorvastatin, and Pravastatin are Equally Effective in Improving Acetylcholine‐Induced Relaxation in STZ‐Diabetic Rats

Abstract

Statin therapy improves cardiovascular (CV) status in normocholesterolemic diabetic patients. To further clarify the underlying mechanisms, we studied and compared the effect of atorvastatin (AV), simvastatin (SV), and pravastatin (PV) (10 mg/kg/day) on acetylcholine (Ach)‐induced relaxation in the aortic rings of streptozotocin (STZ)‐induced diabetic rats. EMAX values for the Ach‐induced relaxation were lower in diabetic than in CT rats (53.70 ± 4.07 % vs. 74.61 ± 3.27 %, N=10, P<0.05). Four weeks of statin treatment improved EMAX in diabetic rats (AV 82.13 ± 7.01 %, SV 84.63 ± 6.51 %, and PV 79.40 ± 9.10 %, N=8, P<0.05), but EC50 values remained unchanged (from 0.41 ± 0.098 μM before treatment to an average across the three statins of 0.54 ± 0.252 μM after treatment, P>;0.05). All statins produced a similar improvement in vascular relaxation. Moreover, this positive statin effect was abolished by 1 mM LNAME, suggesting that it is NO‐dependent. The reduction of CV events by statins in diabetic patients may be secondary to improved endothelial function, which by decreasing vascular tone and systemic vascular resistance, will reduce the workload on the heart. Supported by MBRS‐RISE Grant R25‐GM061838.