Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity

Rajesh G. Mishra, Frank Z. Stanczyk, Kenneth A. Burry, Suzanne Oparil, Benita S. Katzenellenbogen, Michele L. Nealen, John A. Katzenellenbogen, R. Kent Hermsmeyer

Research output: Contribution to journalArticle

Abstract

Previous reports showed that 17β-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 17β-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-β (ER-β) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E 3 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 5α-androstane-3β,17β-diol (3β-Adiol), an endogenous dihydrotestosterone metabolite with ER-β binding activity. R,R-tetrahydrochrysene, a selective ER-β antagonist, significantly blocked the E3- and 3β-Adiol-mediated attenuation of late Ca 2+ signal increases. ER-β 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 3β-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E 3- and 3β-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-β-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.

Original languageEnglish (US)
Pages (from-to)H295-H303
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number1
DOIs
StatePublished - Jan 1 2006

Fingerprint

Thromboxane Receptors
Estrogen Receptors
Primates
Blood Vessels
Muscle Cells
Prostaglandins
Ligands
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Estrogens
Androstane-3,17-diol
Estradiol
Serotonin
Estriol
Dihydrotestosterone
Thromboxanes
Vasoconstrictor Agents
Vasoconstriction
Macaca mulatta
Aorta
Coronary Vessels

Keywords

  • Angiography
  • Calcium
  • Menopause
  • Thromboxane-prostanoid receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity. / Mishra, Rajesh G.; Stanczyk, Frank Z.; Burry, Kenneth A.; Oparil, Suzanne; Katzenellenbogen, Benita S.; Nealen, Michele L.; Katzenellenbogen, John A.; Hermsmeyer, R. Kent.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 290, No. 1, 01.01.2006, p. H295-H303.

Research output: Contribution to journalArticle

Mishra, RG, Stanczyk, FZ, Burry, KA, Oparil, S, Katzenellenbogen, BS, Nealen, ML, Katzenellenbogen, JA & Hermsmeyer, RK 2006, 'Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity', American Journal of Physiology - Heart and Circulatory Physiology, vol. 290, no. 1, pp. H295-H303. https://doi.org/10.1152/ajpheart.00468.2005
Mishra, Rajesh G. ; Stanczyk, Frank Z. ; Burry, Kenneth A. ; Oparil, Suzanne ; Katzenellenbogen, Benita S. ; Nealen, Michele L. ; Katzenellenbogen, John A. ; Hermsmeyer, R. Kent. / Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity. In: American Journal of Physiology - Heart and Circulatory Physiology. 2006 ; Vol. 290, No. 1. pp. H295-H303.
@article{8a7ad73ca61f435b988ced94077ddace,
title = "Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity",
abstract = "Previous reports showed that 17β-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 17β-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-β (ER-β) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E 3 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 5α-androstane-3β,17β-diol (3β-Adiol), an endogenous dihydrotestosterone metabolite with ER-β binding activity. R,R-tetrahydrochrysene, a selective ER-β antagonist, significantly blocked the E3- and 3β-Adiol-mediated attenuation of late Ca 2+ signal increases. ER-β 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 3β-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E 3- and 3β-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-β-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.",
keywords = "Angiography, Calcium, Menopause, Thromboxane-prostanoid receptor",
author = "Mishra, {Rajesh G.} and Stanczyk, {Frank Z.} and Burry, {Kenneth A.} and Suzanne Oparil and Katzenellenbogen, {Benita S.} and Nealen, {Michele L.} and Katzenellenbogen, {John A.} and Hermsmeyer, {R. Kent}",
year = "2006",
month = "1",
day = "1",
doi = "10.1152/ajpheart.00468.2005",
language = "English (US)",
volume = "290",
pages = "H295--H303",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Metabolite ligands of estrogen receptor-β reduce primate coronary hyperreactivity

AU - Mishra, Rajesh G.

AU - Stanczyk, Frank Z.

AU - Burry, Kenneth A.

AU - Oparil, Suzanne

AU - Katzenellenbogen, Benita S.

AU - Nealen, Michele L.

AU - Katzenellenbogen, John A.

AU - Hermsmeyer, R. Kent

PY - 2006/1/1

Y1 - 2006/1/1

N2 - Previous reports showed that 17β-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 17β-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-β (ER-β) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E 3 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 5α-androstane-3β,17β-diol (3β-Adiol), an endogenous dihydrotestosterone metabolite with ER-β binding activity. R,R-tetrahydrochrysene, a selective ER-β antagonist, significantly blocked the E3- and 3β-Adiol-mediated attenuation of late Ca 2+ signal increases. ER-β 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 3β-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E 3- and 3β-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-β-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.

AB - Previous reports showed that 17β-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 17β-estradiol. The purpose of this study was to test whether an endogenous estrogen metabolite with estrogen receptor-β (ER-β) binding activity, estriol (E3), suppresses in vivo and in vitro CH. E 3 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 5α-androstane-3β,17β-diol (3β-Adiol), an endogenous dihydrotestosterone metabolite with ER-β binding activity. R,R-tetrahydrochrysene, a selective ER-β antagonist, significantly blocked the E3- and 3β-Adiol-mediated attenuation of late Ca 2+ signal increases. ER-β 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 3β-Adiol downregulated TPR expression in VMC, which was blocked for both agonists by pretreatment with R,R-tetrahydrochrysene. E 3- and 3β-Adiol-mediated reduction in persistent Ca2+ signals is associated with ER-β-mediated attenuation of TPR expression and may partly explain estrogen benefits in coronary vascular muscle.

KW - Angiography

KW - Calcium

KW - Menopause

KW - Thromboxane-prostanoid receptor

UR - http://www.scopus.com/inward/record.url?scp=33644809888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644809888&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00468.2005

DO - 10.1152/ajpheart.00468.2005

M3 - Article

C2 - 16199482

AN - SCOPUS:33644809888

VL - 290

SP - H295-H303

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 1

ER -