title: Diverse modulating effects of estradiol and progesterone on the monophasic action potential duration in Langendorff-perfused female rabbit hearts.
abstract: This study aimed to comparatively investigate the acute modulating effects of oestrogen and progesterone on the repolarization and the susceptibility of female rabbits to class III anti-arrhythmic agents. The acute influence of estradiol and progesterone on the cardiac repolarization and the drug sensitivity of the rapidly activating delayed rectifier K(+) channel to sotalol was comparatively studied in Langendorff-perfused rabbit hearts at pharmacological concentrations through recording of epicardial monophasic action potentials. In Langendorff-perfused rabbit hearts, estradiol (1-30 μm) concentration-dependently prolonged the monophasic action potential durations (MAPD(30) and MAPD(90) ) (P < 0.05); while the effects of progesterone on MAPD were biphasic: it prolonged MAPD(30) and MAPD(90) at lower concentrations (1-3 μm) but shortened MAPD(30) and MAPD(90) at higher concentrations (10-30 μm). Sotalol-induced prolongation of MAPD(90) was significantly less in the hearts pretreated with progesterone than those treated with estradiol (P < 0.05). The incidence of the pro-arrhythmic events induced by sotalol in the hearts pretreated with progesterone was also significantly lower than those pretreated with estradiol (P < 0.05). In conclusion, estradiol and progesterone have different modulating effects on cardiac repolarization: estradiol can concentration-dependently prolong the cardiac repolarization time and thus may reduce the repolarization reserve and increase the susceptibility of female rabbits to sotalol-induced arrhythmias, whereas progesterone may shorten the cardiac repolarization time at concentrations above 10 μm, thus protecting the heart from drug-induced arrhythmias.
authors.affiliation: Department of Pharmacology, School of Medicine, Tongji University, 1239 Siping Road, Shanghai 200092, China. jcheng@tongji.edu.cn
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cheng
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Su
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D010496:Pericardium / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D012737:Sex Factors; D013015:Sotalol / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D000319:Adrenergic beta-Antagonists; D011374:Progesterone; D004958:Estradiol; D013015:Sotalol