Activation of G protein-coupled estrogen receptor induces endotheliumindependent relaxation of coronary artery smooth muscle

Xuan Yu, Handong Ma, Scott A Barman, Alexander T. Liu, Minga Sellers, John N. Stallone, Eric R. Prossnitz, Richard E. White, Guichun Han

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Estrogens can either relax or contract arteries via rapid, nongenomic mechanisms involving classic estrogen receptors (ER). In addition to ERα and ERβ, estrogen may also stimulate G protein-coupled estrogen receptor 1 (GPER) in nonvascular tissue; however, a potential role for GPER in coronary arteries is unclear. The purpose of this study was to determine how GPER activity influenced coronary artery reactivity. In vitro isometric force recordings were performed on endotheliumdenuded porcine arteries. These studies were augmented by RT-PCR and single-cell patch-clamp experiments. RT-PCR and immunoblot studies confirmed expression of GPER mRNA and protein, respectively, in smooth muscle from either porcine or human coronary arteries. G-1, a selective GPER agonist, produced a concentrationdependent relaxation of endothelium-denuded porcine coronary arteries in vitro. This response was attenuated by G15, a GPER-selective antagonist, or by inhibiting large-conductance calcium-activated potassium (BKCa) channels with iberiotoxin, but not by inhibiting NO signaling. Last, single-channel patch-clamp studies demonstrated that G-1 stimulates BKCa channel activity in intact smooth muscle cells from either porcine or human coronary arteries but had no effect on channels isolated in excised membrane patches. In summary, GPER activation relaxes coronary artery smooth muscle by increasing potassium efflux via BKCa channels and requires an intact cellular signaling mechanism. This novel action of estrogen-like compounds may help clarify some of the controversy surrounding the vascular effects of estrogens.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume301
Issue number5
DOIs
StatePublished - Nov 1 2011

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Estrogen Receptor alpha
G-Protein-Coupled Receptors
Estrogen Receptors
Smooth Muscle
Coronary Vessels
Estrogens
Swine
Arteries
Large-Conductance Calcium-Activated Potassium Channels
Polymerase Chain Reaction
Contracts
Smooth Muscle Myocytes
Endothelium
Blood Vessels
Potassium
Messenger RNA
Membranes

Keywords

  • Calcium-activated potassium channels
  • Coronary
  • G-1
  • G15
  • Selective estrogen receptor modulator

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Activation of G protein-coupled estrogen receptor induces endotheliumindependent relaxation of coronary artery smooth muscle. / Yu, Xuan; Ma, Handong; Barman, Scott A; Liu, Alexander T.; Sellers, Minga; Stallone, John N.; Prossnitz, Eric R.; White, Richard E.; Han, Guichun.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 301, No. 5, 01.11.2011.

Research output: Contribution to journalArticle

Yu, Xuan ; Ma, Handong ; Barman, Scott A ; Liu, Alexander T. ; Sellers, Minga ; Stallone, John N. ; Prossnitz, Eric R. ; White, Richard E. ; Han, Guichun. / Activation of G protein-coupled estrogen receptor induces endotheliumindependent relaxation of coronary artery smooth muscle. In: American Journal of Physiology - Endocrinology and Metabolism. 2011 ; Vol. 301, No. 5.
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