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

K.L. Philp, M. Hussain, N.F. Byrne, M.J. Diver, G. Hart, Susan J. Coker

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages233-242
Number of pages10
JournalBritish Journal of Pharmacology
Volume149
DOIs
Publication statusPublished - 2006

Fingerprint

Estradiol
Muscle Cells
Coronary Occlusion
Sudden Cardiac Death
Gonadal Steroid Hormones
Coronary Vessels
Ventricular Premature Complexes
Patch-Clamp Techniques
Ventricular Fibrillation
Pentobarbital
Intravenous Administration
Cardiac Arrhythmias
Ischemia
Incidence

Keywords

  • arrhythmias
  • myocardial ischaemia
  • L-type calcium current
  • estradiol
  • coronary artery occlusion
  • cardiac myocytes

Cite this

Philp, K.L. ; Hussain, M. ; Byrne, N.F. ; Diver, M.J. ; Hart, G. ; Coker, Susan J. / Greater antiarrhythmic activity of acute 17ß-estradiol in female than male anaesthetized rats: correlation with Ca2+ channel blockade. In: British Journal of Pharmacology. 2006 ; Vol. 149. pp. 233-242.
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abstract = "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.",
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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 journalArticle

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

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DO - 10.1038/sj.bjp.0706850

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SP - 233

EP - 242

JO - British Journal of Pharmacology

T2 - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

ER -