MECHANOINHIBITORY EFFECT OF ESTRADIOL IN GUINEA-PIG URINARY-BLADDER SMOOTH MUSCLES

The mechanoinhibitory effect of estradiol on the myogenic activity of guinea pig urinary bladder detrusor muscles was studied. in detrusor m uscles tonically contracted with 80 mmol/l KCl, 1:7 beta-estradiol and the nonestrogenic isomer 17 alpha-estradiol at 30 mu mol/l reduced th e contraction by 64 +/- 3 and 59 +/- 1%, respectively. In detrusor mus cles maintained in Ca2+- free media and depolarized with 80 mmol/l KCl , the contractile response of muscles to the reintroduction of Ca2+ wa s inhibited in a dose-dependent manner by 17 beta-estradiol, suggestin g that 17 beta-estradiol blocked entry of extracellular Ca2+ into blad der smooth muscle cells and reduced the rise of intracellular Ca2+ req uired for contraction. In detrusor muscles mildly depolarized with 15 mmol/l KCl, 17 beta-estradiol reduced the myogenic activity with an IC 50 of 6.8 +/- 1.3 mu mol/l. The higher activity of 17 beta-estradiol i n this latter test indicated that estradiol could also possess some K channel opening activity. Glibenclamide at 1 mu mol/l did not affect the relaxant activity of 17 beta-estradiol in detrusor muscles stimula ted with 15 mmol/l; however, this activity was diminished in a dose-de pendent manner by iberiotoxin. Collectively, these results have demons trated that in addition to the Ca2+ antagonist activity, 17 beta-estra diol possesses K+ channel opening activity in guinea pig urinary bladd er smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca2+-dependent large-conductance K+ channels.