Involvement of K(ATP) channels in diethylstilbestrol-induced relaxation in rat aorta.

The estrogens prevent cardiovascular diseases that among other effects could be related to the modulation of the vascular tone via modifying ionic channel permeability. ATP-sensitive K(+) (K(ATP)) channels seem to be involved in diethylstilbestrol-induced relaxation in isolated rat aorta precontracted by noradrenaline (30 nM), since the effect is inhibited by glibenclamide (1--10 microM), and 1 mM tetraethylammonium, but not by 30 mM tetraethylammonium or paxilline. The antiestrogen tamoxifen, the inhibitor of protein kinase A, Rp-cAMPS, and the inhibitor of ornithine decarboxylase, difluoromethylornithine, antagonized diethylstilbestrol-induced relaxation. The association of glibenclamide with these compounds separately did not modify the effect of glibenclamide alone on diethylstilbestrol-induced relaxation. Functional K(ATP) channels are present in rat aorta, since diazoxide induced relaxation sensitive to glibenclamide. Papaverine, dibutyryl cyclic AMP and spermine relaxed isolated rat aorta although this was not sensitive to glibenclamide. The relaxation to forskolin was antagonized by glibenclamide. We conclude that diethylstilbestrol-induced relaxation in rat aorta is related to the modulation of K(ATP) channels. Cyclic AMP-dependent mechanisms and polyamine synthesis may mediate this modulation.