Mechanisms of diethylstilbestrol-induced relaxation in rat aorta smooth muscle

The mechanisms of diethylstilbestrol (1 to 30 microM)-induced relaxation on noradrenaline (30 nM)-raised tone in the rat aorta smooth muscle were studied. Neither the increase of calcium content in the medium (3, 6 and 9 mM) nor Bay K 8644 (3, 10 and 100 nM) reversed diethylstilbestrol relaxation. Tamoxifen (3 microM), the quaternary derivate (tamoxifen ethyl bromide, 3 microM), actinomycin D (30 microM), cycloheximide (100 microM), Rp-cAMPS (30 microM), TPCK (1 microM) and difluoromethylornithine (1 mM) inhibited diethylstilbestrol-induced relaxation. Incubation with 2 microg/ml pertussis toxin, propranolol (1 microM), H-7 (10 microM), 2',3'- and 2',5'-dideoxiadenosine (10 and 30 microM, respectively) and methylene blue (10 microM) did not modify diethylstilbestrol-induced relaxation. Our results showed that presumably an activation of membrane mechanisms, protein kinase A activation, genomic mechanisms and polyamine synthesis might participate in diethylstilbestrol-elicited relaxation in addition to the increase in K(ATP) permeability, as previously described. Actinomycin D produces a synergistic effect, with tamoxifen, difluoromethylornithine and glibenclamide antagonizing the effect of diethylstilbestrol. In the case of the association of actinomycin D and glibenclamide, the antagonism of relaxation is complete. The fact that tamoxifen- and difluoromethylornithine-dependent mechanisms participate in diethylstilbestrol relaxation inhibited by glibenclamide suggests that two transduction pathways are involved in the relaxation. Therefore, K(ATP) channels and genomic mechanisms, both modulated by cyclic AMP (cAMP)-dependent mechanisms, are associated with diethylstilbestrol relaxation.