Published Online
on April 23, 2007

A more recent version of this article appeared on June 1, 2007

This Article Full Text (PDF) Data Supplement All Versions of this Article: 49/6/1358    most recent HYPERTENSIONAHA.107.089995v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haas, E. Articles by Barton, M. Search for Related Content PubMed PubMed Citation Articles by Haas, E. Articles by Barton, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL Related Collections Endothelium/vascular type/nitric oxide Other Vascular biology Cell signalling/signal transduction Gene expression

Submitted on February 27, 2007
Revised on March 13, 2007

Differential Effects of 17-Estradiol on Function and Expression of Estrogen Receptor , Estrogen Receptor , 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; and 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.

^* To whom correspondence should be addressed. E-mail: barton{at}usz.ch.

Abstract--Venous complications have been implicated in the adverse effects of hormone replacement therapy. This study investigated acute effects of the natural estrogen, 17-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. 17-Estradiol caused concentration-dependent, endothelium-independent relaxation in arteries (P<0.05 versus solvent control) but not in veins (P not significant). 17-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 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 17-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 17-estradiol in arterial cells only. In summary, this is the first study to report that, in human arteries but not in veins, 17-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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