PRESERVATION OF ENDOTHELIUM-DEPENDENT RELAXATION IN CHOLESTEROL-FED AND STREPTOZOTOCIN-INDUCED DIABETIC MICE BY THE CHRONIC ADMINISTRATION OF CHOLESTYRAMINE

1 Experiments were designed to investigate the effects of the low dens ity lipoprotein (LDL)-lowering drugs cholestyramine on serum LDL level s and endothelium-dependent relaxation to acetylcholine (ACh) in chole sterol-fed or streptozotocin (STZ)-induced diabetic mice. 2 In aortic rings from control mice, ACh or A23187 caused concentration-dependent relaxation. The relaxations caused by ACh or A23187 were significantly attenuated in aortic rings from cholesterol-fed and STZ-diabetic mice . The attenuated vasodilatation in both cholesterol-fed and diabetic m ice was returned to normal by chronic administration of cholestyramine . The endothelium-independent relaxations of aortic rings induced by s odium nitroprusside (SNP) were not significantly different between con trol, cholesterol-fed and STZ-induced diabetic mice. 3 The increased L DL levels in cholesterol-fed and diabetic mice were returned to normal by the chronic administration of cholestyramine. Chronic administrati on of cholestyramine had no effects on serum glucose levels. 4 These r esults suggest that attenuated endothelium-dependent vasodilatations i n both cholesterol-fed and STZ-diabetic mice are improved by the chron ic administration of cholestyramine, and these effects are, at least i n part, due to lowering serum LDL levels.