Published online before print April 30, 2007, doi: 10.1161/HYPERTENSIONAHA.106.081554
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(Hypertension. 2007;49:1364.)
© 2007 American Heart Association, Inc.
Original Articles |
Distinct Roles of Estrogen Receptors 
and ß Mediating Acute Vasodilation of Epicardial Coronary Arteries
From the Department of Internal Medicine (T.T., C.D.S., E.H., I.B., R.M., M.B.), Internal Medicine I, Medical Policlinic, University Hospital Zürich, Zürich, Switzerland; and the Department of Pharmacology (H.L.), Johannes Gutenberg University, Mainz, Germany. Current address: Internal Medicine (T.T.), City Hospital Triemli, Zürich, Switzerland.
Correspondence to Matthias Barton, Department of Internal Medicine, Internal Medicine I, Medical Policlinic, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail barton{at}usz.ch
This study investigated the contribution of estrogen receptors (ERs) 
and ß for epicardial coronary artery function, vascular NO bioactivity, and superoxide (O2–) formation. Porcine coronary rings were suspended in organ chambers and precontracted with prostaglandin F2 to determine direct effects of the selective ER agonists 4,4',4''-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT) or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) or the nonselective ER agonist 17ß-estradiol. Indirect effects on contractility to U46619 and relaxation to bradykinin were assessed and effects on NO, nitrite, and O2– formation were measured in cultured cells. Within 5 minutes, selective ER activation by PPT, but not 17ß-estradiol or the ERß agonist DPN, caused rapid, NO-dependent, and endothelium-dependent relaxation (49±5%; P<0.001 versus ethanol). PPT also caused sustained endothelium- and NO-independent vasodilation similar to 17ß-estradiol after 60 minutes (72±3%; P<0.001 versus ethanol). DPN induced endothelium-dependent NO-independent relaxation via endothelium-dependent hyperpolarization (40±4%; P<0.01 versus ethanol). 17ß-Estradiol and PPT, but not DPN, attenuated the responses to U46619 and bradykinin. All of the ER agonists increased NO and nitrite formation in vascular endothelial but not smooth muscle cells and attenuated vascular smooth muscle cell O2– formation (P<0.001). ER activation had the most potent effects on both nitrite formation and inhibiting O2– (P<0.05). These data demonstrate novel and differential mechanisms by which ER and ERß activation control coronary artery vasoreactivity in males and females and regulate vascular NO and O2– formation. The findings indicate that coronary vascular effects of sex hormones differ with regard to affinity to ER and ERß, which will contribute to beneficial and adverse effects of hormone replacement therapy.
Key Words: atherosclerosis • endothelium • gender • hormone replacement therapy • nitric oxide • vascular smooth muscle
Related Article:
Hypertension 2007 49: 1222-1224.
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  R. D. Feldman and R. Gros Choreographing the Rapid Vascular Effects of Estrogen: Sorting Out the Partners and the Steps Hypertension, June 1, 2007; 49(6): 1222 - 1224. [Full Text] [PDF]
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