Abstract
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.
| Language | English |
|---|---|
| Pages | 233-242 |
| Number of pages | 10 |
| Journal | British Journal of Pharmacology |
| Volume | 149 |
| DOIs | |
| Publication status | Published - 2006 |
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Keywords
- arrhythmias
- myocardial ischaemia
- L-type calcium current
- estradiol
- coronary artery occlusion
- cardiac myocytes
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Greater antiarrhythmic activity of acute 17ß-estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade. / Philp, K.L.; Hussain, M.; Byrne, N.F.; Diver, M.J.; Hart, G.; Coker, Susan J.
In: British Journal of Pharmacology, Vol. 149, 2006, p. 233-242.Research output: Contribution to journal › Article
TY - JOUR
T1 - Greater antiarrhythmic activity of acute 17ß-estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade
AU - Philp, K.L.
AU - Hussain, M.
AU - Byrne, N.F.
AU - Diver, M.J.
AU - Hart, G.
AU - Coker, Susan J.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - arrhythmias
KW - myocardial ischaemia
KW - L-type calcium current
KW - estradiol
KW - coronary artery occlusion
KW - cardiac myocytes
UR - http://dx.doi.org/10.1038/sj.bjp.0706850
U2 - 10.1038/sj.bjp.0706850
DO - 10.1038/sj.bjp.0706850
M3 - Article
VL - 149
SP - 233
EP - 242
JO - British Journal of Pharmacology
T2 - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
ER -