Vascular effects of estrone and diethylstilbestrol in porcine coronary arteries

Abstract

Objective: 

To explore the effects of different estrogens on vascular function, we compared the vasorelaxant effects of 17β-estradiol, 17α-estradiol, estrone, and the synthetic estrogen diethylstilbestrol (DES) on porcine coronary arterial segments.

Design: 

Porcine coronary arterial rings were contracted with the stable thromboxane A₂ analogue U46619 (3 × 10⁻⁸ M), and direct relaxation was examined by the addition of increasing concentrations of 17β-estradiol, 17α-estradiol, estrone, or DES (10⁻⁹ to 10⁻⁴ M). Modulation of agonist-induced contraction and relaxation was studied in coronary arterial rings incubated for 20 minutes with DES or estrone (10⁻¹⁰-10⁻⁶ M) with 17β-estradiol (10⁻⁹ M) as comparison.

Results: 

Direct relaxation of arterial rings potentiated by these estrogens was recorded with a rank order potency of DES > 17β-estradiol > estrone > 17α-estradiol. 17β-Estradiol potentiated relaxation responses to sodium nitroprusside and levcromakalim but not bradykinin or A23187 while reducing contractions to 5-hydroxytryptamine and U46619. DES and estrone, both at 10⁻⁶ M, mimicked the 17β-estradiol-potentiated sodium nitroprusside and levcromakalim relaxation responses. Additionally, the inhibitory effects of 17β-estradiol (10⁻⁹ M) on 5-hydroxytryptamine- and U46619-induced contractions were partially reproducible by DES (10⁻⁶ M) and estrone (10⁻⁶ M).

Conclusions: 

Although DES is the most potent among the tested estrogenic compounds in eliciting relaxation, 17β-estradiol is more effective than estrone and DES at enhancing endothelium-independent relaxation and reducing vascular contraction in porcine coronary arteries.

In Brief

Enhancement of relaxations and impairment of contractions caused by acute treatment with physiological concentrations of 17 β-estradiol in porcine coronary arteries can only be mimicked by much higher sub pharmacological concentrations of DES and estrone.