Enhanced responses to 17beta-estradiol in rat hearts treated with isoproterenol: involvement of a cyclic AMP-dependent pathway.
We determined the effects of 17beta-estradiol, the most effective estrogen, acutely administered, on the heart/ventricular myocyte with or without treatment with isoproterenol (Iso). At 0.1 to 1 nM, 17beta-estradiol, which itself had no effect, reduced the heart rate and developed pressures in the isolated perfused heart treated with 10(-7) M Iso. One nanomolar 17beta-estradiol also inhibited the cyclic AMP (cAMP) production in Iso-treated ventricular myocytes. At 10 nM to 1 microM, 17beta-estradiol itself reduced the heart rate and incidence of ischemia/reperfusion-induced arrhythmias, with the exception of diastolic pressure. The effects of 17beta-estradiol on heart rate, systolic and mean pressures, and arrhythmias were significantly enhanced in the heart/ventricular myocyte treated with Iso. Tamoxifen, an estrogen receptor antagonist, did not antagonize the effect of 17beta-estradiol on the Ca(2+) current in ventricular myocytes treated with Iso, nor did it alter the effect of the hormone on the cAMP production augmented by Iso and forskolin. The effects of 17beta-estradiol on Ca(2+) current in the presence or absence of tamoxifen and/or Iso were similar in male rats, which do not possess the estrogen receptor, and female rats, which have the estrogen receptor. In conclusion, we have shown for the first time that estrogen at physiological concentrations modulates negatively the stimulatory actions of Iso on the heart rate and cardiac contractility. The effects may result from activation of an unknown membrane receptor and the adenylate cyclase/cAMP pathway, which enhances Ca(2+) influx across the L-type Ca(2+) channel.
Li
H Y
HY
Department of Physiology and Institute of Cardiovascular Sciences and Medicine, Faculty of Medicine, The University of Hong Kong.
Bian
J S
JS
Kwan
Y W
YW
Wong
T M
TM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D010052:Ovariectomy; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D004965:Estrogen Antagonists; D013629:Tamoxifen; D004958:Estradiol; D000242:Cyclic AMP; D007545:Isoproterenol