Mechanisms involved in the relaxant effect of estrogens on rat aorta strips.
The effects of estrogens 17beta-estradiol (17beta-E2), 17alpha-estradiol (17alpha-E2) and diethylstilbestrol (DES) on CaCl2 (3mM)-induced contractions on rat aorta strips have been assayed. Both 17alpha-E2 and DES, but not the 17beta-E2 relaxed and inhibited the contraction induced by CaCl2. The antiestrogen tamoxifen (0.1, 1 and 3 microM) antagonizes, in a concentration-dependent way, the relaxant effect of 17alpha-E2 but the relaxation induced by DES is only significantly antagonized with 3 microM of tamoxifen. Cycloheximide (0.1 and 0.3 mM) does not modify the 17alpha-E2 or DES effects. However, the inhibitors of cAMP-dependent protein kinase TPCK (1 microM) and Rp-cAMPS (10 microM) inhibit the relaxation induced by 17alpha-E2 and DES. The elimination of endothelium by rubbing, significantly inhibits the effect of DES but does not modify the effect of 17alpha-E2. Our results suggest that estrogen-induced relaxation is a non-genomic effect possibly or presumably produced by activation of estrogenic receptors and mediated by cAMP. The DES-effect is partially endothelium-dependent but the effect of 17alpha-E2 is independent of endothelium.
Rodriguez
J
J
Laboratorio de Farmacologia, Dpto. Medicina, Facultad de Medicina, Oviedo, Spain.
Garcia de Boto
M J
MJ
Hidalgo
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002122:Calcium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology
D015220:Calcium Channels; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002122:Calcium Chloride