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Metabolite ligands of estrogen receptor-beta reduce primate coronary hyperreactivity.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2006 Jan; Vol. 290 (1), pp. H295-303. Date of Electronic Publication: 2005 Sep 30. - Publication Year :
- 2006
-
Abstract
- Previous reports showed that 17beta-estradiol implants attenuate in vivo coronary hyperreactivity (CH), characterized by long-duration vasoconstrictions (in coronary angiographic experiments), in menopausal rhesus monkeys. Prolonged Ca2+ contraction signals that correspond with CH in coronary vascular muscle cells (VMC) to the same dual-constrictor stimulus, serotonin + the thromboxane analog U-46619, in estrogen-deprived VMC were suppressed by >72 h in 17beta-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-beta (ER-beta) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E3 treatment in vivo for 4 wk significantly attenuated the angiographically evaluated vasoconstrictor response to intracoronary serotonin + U-46619 challenge. In vitro treatment of rhesus coronary VMC for >72 h with nanomolar E3 attenuated late Ca2+ signals. This reduction of late Ca2+ signals also appeared after >72 h of treatment with subnanomolar 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), an endogenous dihydrotestosterone metabolite with ER-beta binding activity. R,R-tetrahydrochrysene, a selective ER-beta antagonist, significantly blocked the E3- and 3beta-Adiol-mediated attenuation of late Ca2+ signal increases. ER-beta and thromboxane-prostanoid receptor (TPR) were coexpressed in coronary arteries and aorta. In vivo E3 treatment attenuated aortic TPR expression. Furthermore, in vitro treatment with E3 or 3beta-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E3- and 3beta-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-beta-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.
- Subjects :
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology
Administration, Cutaneous
Androstane-3,17-diol pharmacology
Animals
Calcium Signaling drug effects
Chrysenes pharmacology
Coronary Vasospasm chemically induced
Estriol administration & dosage
Estriol pharmacology
Estrogen Receptor beta agonists
Estrogen Receptor beta antagonists & inhibitors
Female
Gene Expression drug effects
Genistein pharmacology
Macaca mulatta
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular drug effects
Nitriles pharmacology
Propionates pharmacology
Receptors, Thromboxane biosynthesis
Serotonin pharmacology
Vasoconstriction drug effects
Coronary Vasospasm drug therapy
Estriol therapeutic use
Estrogen Receptor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 290
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16199482
- Full Text :
- https://doi.org/10.1152/ajpheart.00468.2005