Vascular effects of estrone and diethylstilbestrol in porcine coronary arteries

Abstract

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.

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.

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).

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.