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

Objectives: While alterations in cholesterol and lipoprotein profiles partl y account for menopause being a risk factor for coronary heart disease, rec ent 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 vas cular function in isolated porcine coronary artery rings. Concomitantly, we sought to determine if physiological concentrations of 17 beta-estradiol c ould acutely potentiate relaxation. Results: 17 alpha- and 17 beta-estradio l at pharmacological (>1 mu M) 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 eli cited by cromakalim, levcromakalim and sodium nitroprusside, but not bradyk inin or calcium ionophore A23187, were significantly enhanced. This potenti ating action was also insensitive to tamoxifen and ICI 182780. Our data pro vide evidence for an acute indirect relaxant action of 17 beta-estradiol an d suggest that it may be via a tamoxifen- and ICI 182780-insensitive estrog en receptor. While this response was only observed at pharmacological conce ntrations, the potentiation of cromakalim, levcromakalim and sodium nitropr usside relaxation was evident in the presence of a physiological concentrat ion (1 nM) of 17 beta-estradiol. Conclusions: These results demonstrate tha t 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. (C) 1999 Elsevier Science BN. All rights reserved.