Mechanisms underlying the chronic pravastatin treatment-induced improvement in the impaired endothelium-dependent aortic relaxation seen in streptozotocin-induced diabetic rats.

ABSTRACT: 1. We investigated the effects of chronic pravastatin treatment on the impaired endothelium-dependent relaxation seen in aortae from established streptozotocin (STZ)-induced diabetic rats. Starting at 6 weeks of diabetes, pravastatin (10 mg kg(-1)) was administered to STZ-induced diabetic rats for 4 weeks. 2. The increased total cholesterol and low-density lipoprotein (LDL) cholesterol levels seen in STZ-induced diabetic rats were not restored to normal by pravastatin. Aortae from pravastatin-treated diabetic rats did not show an impaired endothelium-dependent relaxation to acetylcholine. The expression of the mRNA for endothelial nitric oxide synthase was unaffected by diabetes or pravastatin. 3. The enhanced level of malondialdehyde (MDA)-modified LDL seen in STZ-induced diabetic rats was normalized by pravastatin treatment. The resistance of LDL to oxidation was assessed by measuring the amount of MDA or conjugated dienes generated by incubation with copper ions. LDL isolated from diabetic rats, but not those from pravastatin-treated diabetics, showed enhanced the susceptibility to oxidation, but incubation in vitro with pravastatin had no effect on LDL oxidation. 4. Following incubation of control aortae for 6 h with LDL (0.1 mg protein ml(-1)) isolated from diabetic rats, the endothelium-dependent relaxation to acetylcholine or A23187 was impaired, but LDL isolated from control or pravastatin-treated rats had no such effect. This inhibitory effect of diabetic LDL was prevented by superoxide dismutase (SOD), a superoxide scavenger. 5. These results suggest that pravastatin preserves endothelial function in aortae from STZ-induced diabetic rats without lowering plasma cholesterol, and its effect may be due to decreased LDL oxidation.

SUBMITTER: Kobayashi T 

PROVIDER: S-EPMC1572325 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature