Endothelin-1 and nitric oxide levels are related to cardiovascular risk factors but are not modified by estradiol replacement in healthy postmenopausal women. A cross-sectional and a randomized cross-over study

Objective: To evaluate whether in healthy postmenopausal women endothelial substances such as endothelin-1 (ET-1) and nitric oxide are related to cardiovascular risk factors and can be influenced by estradiol replacement. Design: A cross-sectional evaluation and a randomized, double-blind, placebo-controlled study with cross-over. Methods: In 20 healthy postmenopausal women it was investigated the relation of ET-1 and NOx with age, BMI, 24-h blood pressure, lipid and glucose metabolism, and coagulation parameters. In addition, in the same women, the role played by estrogens on circulating ET-1 and stable derivatives of nitric oxide (nitrite/nitrates) was investigated by administering for 2 months transdermal estradiol (50 μg/day) vs. placebo. Results: ET-1 and NOx were inversely related to each other ( r=0.458; P=0.016). Multivariate analysis of regression showed that ET-1 levels were related directly to LDL-cholesterol ( r=0.585; P=0.0005) and protein C ( r=0.516; P=0.0008), and inversely to insulin ( r=0.488; P=0.0065). The ratio NOx/ET-1 was directly related to HDL-cholesterol ( r=0.441; P=0.005). The above relations were not influenced by estradiol. Indeed, in comparison to placebo, transdermal estradiol, besides reducing nocturnal systolic ( P=0.002) and diastolic ( P=0.03) blood pressure, did not modify ET-1 or NOx levels, as well as, any of the parameters considered. Conclusions: The relation of several cardiovascular risk factors with ET-1 and NOx/ET-1 suggests a primary role for these endothelial products in the determination of the cardiovascular risk of women. The present data do not support a role for transdermal estradiol in modifying ET-1 or NOx levels of healthy postmenopausal women.