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(Hypertension. 2007;49:1358.)
© 2007 American Heart Association, Inc.

Original Articles

Differential Effects of 17ß-Estradiol on Function and Expression of Estrogen Receptor , Estrogen Receptor ß, and GPR30 in Arteries and Veins of Patients With Atherosclerosis

Elvira Haas; Matthias R. Meyer; Ulrich Schurr; Indranil Bhattacharya; Roberta Minotti; Hung H. Nguyen; Andres Heigl; Mario Lachat; Michele Genoni; Matthias Barton

From the Department of Internal Medicine (E.H., M.R.M., I.B., R.M., H.H.N., A.H., M.B.), Internal Medicine I, Medical Policlinic, Zurich, Switzerland; and the Clinic for Cardiovascular Surgery (U.S., M.L., M.G.), University Hospital Zurich, Zurich, Switzerland.

Correspondence to Matthias Barton, University Hospital Zürich, Department of Internal Medicine, Internal Medicine I, Medical Policlinic, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail barton{at}usz.ch

Venous complications have been implicated in the adverse effects of hormone replacement therapy. This study investigated acute effects of the natural estrogen, 17ß-estradiol, on function, estrogen receptors/GPR30 expression, and kinase activation in vascular rings and cultured smooth muscle cells from arteries and veins of patients with coronary artery disease. Changes in vascular tone of internal mammary arteries and saphenous veins exposed to the steroid were recorded. 17ß-Estradiol caused concentration-dependent, endothelium-independent relaxation in arteries (P<0.05 versus solvent control) but not in veins (P not significant). 17ß-Estradiol enhanced contractions to endothelin-1 in veins but not in arteries. The novel membrane estrogen receptor GPR30 was detected in both vessels. Moreover, gene expression of estrogen receptor ß was 10-fold higher than that of estrogen receptor or GPR30 (P<0.05). Expression of all 3 of the receptors was reduced after exposure to 17ß-estradiol in arteries but not in veins (P<0.05). Basal phosphorylation levels of extracellular signal-regulated kinase were higher in venous than in arterial smooth muscle cells and were increased by 17ß-estradiol in arterial cells only. In summary, this is the first study to report that, in human arteries but not in veins, 17ß-estradiol acutely affects vascular tone, estrogen receptor expression, including GPR30, and extracellular signal-regulated kinase phosphorylation. These data indicate that effects of natural estrogens in humans differ between arterial and venous vascular beds, which may contribute to the vascular risks associated with menopause or hormone therapy.

Key Words: aromatase • bypass graft • clinical study • gender • hormone replacement therapy • human • 5-reductase

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