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 density lipoprotein (LDL)-lowering drugs cholestyramine on serum LDL levels and endothelium-dependent relaxation to acetylcholine (ACh) in cholesterol-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 mice was returned to normal by chronic administration of cholestyramine. The endothelium-independent relaxations of aortic rings induced by sodium nitroprusside (SNP) were not significantly different between control, cholesterol-fed and STZ-induced diabetic mice. 3. The increased LDL levels in cholesterol-fed and diabetic mice were returned to normal by the chronic administration of cholestyramine. Chronic administration of cholestyramine had no effects on serum glucose levels. 4. These results suggest that attenuated endothelium-dependent vasodilatations in both cholesterol-fed and STZ-diabetic mice are improved by the chronic administration of cholestyramine, and these effects are, at least in part, due to lowering serum LDL levels.