Effect of endogenous estrogen on endothelial function in women with coronary heart disease and its mechanism

BACKGROUND: Estrogen promotes and modulates vascular endothelial function, which may be protective against development of atherosclerosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been reported to be associated with the impairment of vascular endothelial function. Recent studies suggested estrogen replacement therapy lowers plasma concentrations of ADMA in healthy postmenopausal women. However, the relation between endogenous estrogen and ADMA and their effect on endothelial function in patients with coronary heart disease (CHD) remains unclear. METHODS: Flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of the brachial arteries were detected by using high-resolution ultrasound in 33 women with CHD and 17 healthy controls. Plasma estradiol, ADMA, and lipid concentrations were also measured in all subjects. RESULTS: In comparison with control group, FMD and NID were significantly decreased in the CHD group (1.73 +/- 1.26% vs. 5.37 +/- 3.20%, p < 0.001 and 12.38 +/- 6.70% vs. 20.79 +/- 7.57%, p < 0.01, respectively). Plasma estradiol concentrations in the CHD group were lower than in controls (27.80 +/- 12.28 vs. 43.83 +/- 14.30 pg/ml, p < 0.01), whereas ADMA concentrations in the CHD group were higher than in controls (3.39 +/- 1.07 vs. 1.31 +/- 0.69 micromol/l, p < 0.001). Pearson correlation analysis determined that plasma estradiol concentrations were associated with FMD, NID, age, systolic pressure, diastolic pressure and ADMA (r = 0.610, p < 0.01; r = 0.392, p < 0.01; r = -0.589, p < 0.01; r= -0.364, p < 0.01; r = -0.350, p < 0.05; r = -0.553, p < 0.01; respectively). Multiple linear stepwise regression analysis revealed that plasma estradiol concentrations was independently positively correlated with FMD (p < 0.005) and negatively correlated with ADMA (p < 0.05). CONCLUSIONS: Both FMD and NID are impaired in women with CHD. The decrease of endogenous estrogen concentrations and the increase of ADMA concentrations may involve the endothelial dysfunction in women with CHD.