MECHANISMS INVOLVED IN THE RELAXANT EFFECT OF ESTROGENS ON RAT AORTA STRIPS

The effects of estrogens 17 beta-estradiol (17 beta-E(2)), 17 alpha-es tradiol (17 alpha-E(2)) and diethylstilbestrol (DES) on CaCl2 (3mM)-in duced contractions on rat aorta strips have been assayed. Both 17 alph a-E(2) and DES, but not the 17 beta-E(2) relaxed and inhibited the con traction induced by CaCl2. The antiestrogen tamoxifen (0.1, 1 and 3 mu M) antagonizes, in a concentration-dependent way, the relaxant effect of 17 alpha-E(2) but the relaxation induced by DES is only significan tly antagonized with 3 mu M of tamoxifen. Cycloheximide (0.1 and 0.3 m M) does not modify the 17 alpha-E(2) or DES effects. However, the inhi bitors of cAMP-dependent protein kinase TPCK (1 mu M) and Rp-cAMPS (10 mu M) inhibit the relaxation induced by 17 alpha-E(2) and DES. The el imination of endothelium by rubbing, significantly inhibits the effect of DES but does not modify the effect of 17 alpha-E(2). Our results s uggest that estrogen-induced relaxation is a non-genomic effect possib ly or presumably produced by activation of estrogenic receptors and me diated by cAMP. The DES-effect is partially endothelium-dependent but the effect of 17 alpha-E(2) is independent of endothelium.