Dilation of epicardial coronary arteries by the G protein-coupled estrogen receptor agonists G-1 and ICI 182,780

Pharmacology. 2010;86(1):58-64. doi: 10.1159/000315497. Epub 2010 Jul 17.


Endogenous estrogens protect from coronary artery disease in premenopausal women, but the mechanisms involved are only partly understood. This study investigated whether activation of the novel G protein-coupled estrogen receptor (GPER, formerly known as GPR30) affects coronary artery tone, and whether this is affected by concomitant blockade of estrogen receptors (ER) alpha and beta. Rings of epicardial porcine coronary arteries suspended in organ chambers were precontracted with prostaglandin F(2)alpha, and direct effects of G-1 (GPER agonist) and ICI 182,780 (GPER agonist and ERalpha/ERbeta antagonist) were determined. In addition, indirect effects on contractility to endothelin-1 and serotonin (a vasoconstrictor released from aggregating platelets during acute myocardial infarction) were assessed. ICI 182,780 and G-1 caused acute dilation of coronary arteries to a comparable degree (p < 0.05 vs. solvent control). Both GPER agonists attenuated contractions to endothelin-1 (p < 0.05 vs. ethanol), but not to serotonin (n.s.). In summary, these findings provide evidence for direct and indirect coronary artery dilator effects of GPER independent of ERalpha and ERbeta, and are the first demonstration of arterial vasodilation in response to ICI 182,780.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology
  • Cyclopentanes / pharmacology*
  • Endothelin-1 / pharmacology
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / agonists*
  • Estrogen Receptor alpha / antagonists & inhibitors
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / agonists*
  • Estrogen Receptor beta / antagonists & inhibitors
  • Estrogen Receptor beta / metabolism
  • Fulvestrant
  • In Vitro Techniques
  • Pericardium / drug effects*
  • Pericardium / physiology
  • Quinolines / pharmacology*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Serotonin / pharmacology
  • Swine
  • Vasodilation / drug effects*


  • 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
  • Cyclopentanes
  • Endothelin-1
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Quinolines
  • Receptors, G-Protein-Coupled
  • Fulvestrant
  • Serotonin
  • Estradiol