Short-term exposure to physiological levels of 17 beta-estradiol enhances endothelium-independent relaxation in porcine coronary artery

Cardiovasc Res. 1999 Apr;42(1):224-31. doi: 10.1016/s0008-6363(98)00265-x.

Abstract

Objectives: While alterations in cholesterol and lipoprotein profiles partly account for menopause being a risk factor for coronary heart disease, recent studies have suggested that 17 beta-estradiol may have vascular effects. Our aims were to study the short-term effects of 17 beta-estradiol on vascular function in isolated porcine coronary artery rings. Concomitantly, we sought to determine if physiological concentrations of 17 beta-estradiol could acutely potentiate relaxation

Results: 17 alpha- and 17 beta-estradiol at pharmacological (> 1 microM) concentrations produced relaxation in U46619-pre-contracted porcine coronary artery rings. Relaxation evoked by 17 beta-estradiol was not reversed by the estrogen receptor antagonists tamoxifen and ICI 182780. Following 20 min exposure to a physiological concentration of 17 beta-estradiol (1 nM), which on its own had no effect, relaxation elicited by cromakalim, levcromakalim and sodium nitroprusside, but not bradykinin or calcium ionophore A23187, were significantly enhanced. This potentiating action was also insensitive to tamoxifen and ICI 182780. Our data provide evidence for an acute indirect relaxant action of 17 beta-estradiol and suggest that it may be via a tamoxifen- and ICI 182780-insensitive estrogen receptor. While this response was only observed at pharmacological concentrations, the potentiation of cromakalim, levcromakalim and sodium nitroprusside relaxation was evident in the presence of a physiological concentration (1 nM) of 17 beta-estradiol.

Conclusions: These results demonstrate that short-term exposure to 17 beta-estradiol, at concentrations that have no effect on their own, can enhance vasorelaxation. These vascular effects may partly account for some of the acute effects of 17 beta-estradiol on blood flow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Animals
  • Coronary Vessels / drug effects*
  • Cromakalim / pharmacology
  • Drug Synergism
  • Endothelium, Vascular / drug effects*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology*
  • Estrogen Antagonists / pharmacology
  • Female
  • Fulvestrant
  • In Vitro Techniques
  • Male
  • Nitroprusside / pharmacology
  • Swine
  • Tamoxifen / pharmacology
  • Time Factors
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects*

Substances

  • Estrogen Antagonists
  • Vasoconstrictor Agents
  • Tamoxifen
  • Cromakalim
  • Nitroprusside
  • Fulvestrant
  • Estradiol
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid