Mechanisms underlying improvement of impaired endothelium-dependent relaxation in STZ-induced diabetic rats by chronic pravastatin treatment

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.166-166
• Main Authors: Kobayashi, Tsuneo, Kamata, Katsuo
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34679-7

This study was designed to investigate the effects of chronic pravastatin(10 mg/kg) treatment on impaired endothelium-dependent relaxation of aortae from established STZ-induced diabetes. The increased total cholesterol and LDL cholesterol levels seen in diabetes were not restored by the chronic administration of pravastatin. Aortae from diabetes showed an impaired response to relaxation to ACh, which was prevented by administration of pravastatin. The increased oxidation levels of plasma LDL seen in diabetes were normalized, but plasma lipid peroxidation was not affected by the administration of pravastatin. LDL isolated from diabetes enhanced the susceptibility to oxidation (TBARS) of LDL compared to control. Chronic administration of pravastatin inhibited the oxidation of LDL compared to diabetic but incubation in in vitro of pravastatin had no effect on LDL oxidation. In incubation for 6hr of VLDL and LDL (0.2mg protein /ml) isolated from diabetes, relaxation to ACh showed an impaired response to compared. These results suggest that pravastatin preserves endothelial dysfunction in aorta from diabetic rats without lowering cholesterols, and this may be due to decreased LDL oxidation. It is further suggested that incubation of aortic strips with circulating VLDL and LDL isolated from diabetic can impair the endothelium-dependent relaxation.