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 muscles tonically contracted with 80 mmol/l KCl, 1:7 beta-estradiol and the nonestrogenic isomer 17 alpha-estradiol at 30 mu mol/l reduced the contraction by 64 +/- 3 and 59 +/- 1%, respectively. In detrusor muscles maintained in Ca2+- free media and depolarized with 80 mmol/l KCl, the contractile response of muscles to the reintroduction of Ca2+ was inhibited in a dose-dependent manner by 17 beta-estradiol, suggesting that 17 beta-estradiol blocked entry of extracellular Ca2+ into bladder smooth muscle cells and reduced the rise of intracellular Ca2+ required for contraction. In detrusor muscles mildly depolarized with 15 mmol/l KCl, 17 beta-estradiol reduced the myogenic activity with an IC50 of 6.8 +/- 1.3 mu mol/l. The higher activity of 17 beta-estradiol in 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 stimulated with 15 mmol/l; however, this activity was diminished in a dose-dependent manner by iberiotoxin. Collectively, these results have demonstrated that in addition to the Ca2+ antagonist activity, 17 beta-estradiol possesses K+ channel opening activity in guinea pig urinary bladder smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca2+-dependent large-conductance K+ channels.