Greater antiarrhythmic activity of acute 17β‐estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade

Background and purpose: Female sex hormones may protect pre‐menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17β‐estradiol, on ischaemia‐induced cardiac arrhythmias and on the L‐type Ca2+ current (ICaL). Experimental approach: In vivo...

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Published in:British journal of pharmacology 2006-10, Vol.149 (3), p.233-242
Main Authors: Philp, K L, Hussain, M, Byrne, N F, Diver, M J, Hart, G, Coker, S J
Format: Article
Language:English
Subjects:
arrhythmias
cardiac myocytes
coronary artery occlusion
estradiol
L‐type calcium current
myocardial ischaemia
Research Papers
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Summary:Background and purpose: Female sex hormones may protect pre‐menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17β‐estradiol, on ischaemia‐induced cardiac arrhythmias and on the L‐type Ca2+ current (ICaL). Experimental approach: In vivo experiments were performed in pentobarbital‐anaesthetized rats subjected to acute coronary artery occlusion. ICaL was measured by the whole‐cell patch‐clamp technique, in rat isolated ventricular myocytes. Key results: Acute intravenous administration of 17β‐estradiol as a bolus dose followed by a continuous infusion, commencing 10 min before coronary artery occlusion, had dose‐dependent antiarrhythmic activity. In female rats 300 ng kg‐1 + 30 ng kg−1 min−1 17β‐estradiol significantly reduced the number of ventricular premature beats (VPBs) and the incidence of ventricular fibrillation (VF). A ten fold higher dose of 17β‐estradiol was required to cause similar effects in male rats. In vitro 17β‐estradiol reduced peak ICaL in a concentration‐dependent manner. The EC50 was ten‐fold higher in male myocytes (0.66 μM) than in females (0.06 μM). Conclusions and implications: These results indicate that 17β‐estradiol has marked dose‐dependent antiarrhythmic activity that is greater in female rats than in males. A similar differential potency in blocking ICaL in myocytes from female and male rats can account for this effect. This provides an explanation for the antiarrhythmic activity of 17β‐estradiol and gender‐selective protection against sudden cardiac death. British Journal of Pharmacology (2006) 149, 233–242. doi:10.1038/sj.bjp.0706850
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0706850