Greater antiarrhythmic activity of acute 17beta-estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade.
OBJECTIVE
Female sex hormones may protect pre-menopausal women from sudden cardiac death. We therefore investigated the effects of the main female sex hormone, 17beta-estradiol, on ischaemia-induced cardiac arrhythmias and on the L-type Ca2+ current (ICaL).


METHODS
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.


RESULTS
Acute intravenous administration of 17beta-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) 17beta-estradiol significantly reduced the number of ventricular premature beats (VPBs) and the incidence of ventricular fibrillation (VF). A ten fold higher dose of 17beta-estradiol was required to cause similar effects in male rats. In vitro 17beta-estradiol reduced peak ICaL in a concentration-dependent manner. The EC50 was ten-fold higher in male myocytes (0.66 microM) than in females (0.06 microM).


CONCLUSIONS
These results indicate that 17beta-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 17beta-estradiol and gender-selective protection against sudden cardiac death.
Philp
K L
KL
Department of Pharmacology and Therapeutics, UK.
Hussain
M
M
Byrne
N F
NF
Diver
M J
MJ
Hart
G
G
Coker
S J
SJ
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000150:complications; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D004958:Estradiol