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Diverse modulating effects of estradiol and progesterone on the monophasic action potential duration in Langendorff‐perfused female rabbit hearts
Author(s) -
Cheng Jianhua,
Ma Xiaohong,
Zhang Juan,
Su Dan
Publication year - 2012
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2010.00911.x
Subject(s) - medicine , sotalol , repolarization , endocrinology , estrogen , chemistry , electrophysiology , atrial fibrillation
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 μ m ) 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 μ m ) but shortened MAPD 30 and MAPD 90 at higher concentrations (10–30 μ m ). 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 μ m , thus protecting the heart from drug‐induced arrhythmias.