17beta-estradiol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level

Previous studies have shown that endothelial dysfunction is associated to an increase of endogenous nitric oxide synthase (NOS) inhibitor level and estrogen reduces impairment of the endothelium due to oxidized low-density lipoprotein (LDL). The purpose of the present study was to investigate the effect of estradiol on endothelial dysfunction and the increased level of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, induced by LDL. Male Sprague-Dawley rats were treated with a single injection of native LDL (4 mg/kg) for 48 h. Vasodilator responses to acetylcholine in the aortic rings and serum levels of ADMA and malondialdehyde (MDA) were determined. Treatment with native LDL markedly reduced endothelium-dependent relaxation to acetylcholine in the isolated rat thoracic aortic rings and increased serum levels of ADMA and MDA (P < 0.01). Pretreatment with 17beta-estradiol (0.1 or 0.3 mg/kg) significantly attenuated inhibition of vasodilator responses to acetylcholine and elevation of both ADMA and MDA concentration by LDL (P < 0.01). These results suggest that estradiol possesses a protective effect on the endothelium and the protective effect is related to reduction of ADMA concentration by inhibition of lipid peroxidation.