title: 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.
abstract: 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.
  
  
  METHODS
  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 microg/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.
authors.affiliation: Institute of Obstetrics and Gynecology of Modena, University of Modena, Modena, Italy. cagnacci@unimore.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Cagnacci
authors.forename: Roberto
authors.initials: R
authors.lastname: Tarquini
authors.forename: Federico
authors.initials: F
authors.lastname: Perfetto
authors.forename: Serenella
authors.initials: S
authors.lastname: Arangino
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Zanni
authors.forename: Paolo
authors.initials: P
authors.lastname: Cagnacci
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchinetti
authors.forename: Annibale
authors.initials: A
authors.lastname: Volpe
mesh_terms: D000279:Administration, Cutaneous; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL; D018592:Cross-Over Studies; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood*; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D017698:Postmenopause; D011486:Protein C / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019332:Endothelin-1; D007328:Insulin; D011486:Protein C; D009569:Nitric Oxide; D004958:Estradiol