Li H Y, Bian J S, Kwan Y W, Wong T M
Department of Physiology and Institute of Cardiovascular Sciences and Medicine, Faculty of Medicine, The University of Hong Kong.
J Pharmacol Exp Ther. 2000 May;293(2):592-8.
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.
我们测定了急性给予最有效的雌激素17β-雌二醇对有无异丙肾上腺素（Iso）处理的心脏/心室肌细胞的影响。在0.1至1 nM时，本身无作用的17β-雌二醇可降低用10⁻⁷ M Iso处理的离体灌注心脏的心率和发展压力。1 nM的17β-雌二醇还可抑制Iso处理的心室肌细胞中环磷酸腺苷（cAMP）的产生。在10 nM至1 μM时，17β-雌二醇本身可降低心率以及缺血/再灌注诱导的心律失常的发生率，但舒张压除外。在Iso处理的心脏/心室肌细胞中，17β-雌二醇对心率、收缩压和平均压以及心律失常的影响显著增强。雌激素受体拮抗剂他莫昔芬既不拮抗17β-雌二醇对Iso处理的心室肌细胞中钙电流的影响，也不改变该激素对Iso和福斯可林增强的cAMP产生的影响。在不具有雌激素受体的雄性大鼠和具有雌激素受体的心雌性大鼠中，17β-雌二醇在有无他莫昔芬和/或Iso存在时对钙电流的影响相似。总之，我们首次表明生理浓度的雌激素可负向调节Iso对心率和心脏收缩力的刺激作用。这些作用可能是由于激活了一种未知的膜受体以及腺苷酸环化酶/cAMP途径，从而增强了L型钙通道的钙内流。
