Abstract
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/lKCl, 17 beta-estradiol and the nonestrogenic isomer 17 alpha-estradiol at 30 mumol/l reduced the contraction by 64 +/- 3 and 59 +/- 1%, respectively. In detrusor muscles maintained in Ca(2+)-free media and depolarized with 80 mmol/lKCl, 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/lKCl, 17 beta-estradiol reduced the myogenic activity with an IC50 of 6.8 +/- 1.3 mumol/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 mumol/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...Continue Reading
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