Drici M D, Burklow T R, Haridasse V, Glazer R I, Woosley R L
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
Circulation. 1996 Sep 15;94(6):1471-4. doi: 10.1161/01.cir.94.6.1471.
Sex hormones are known to exert direct and indirect effects on cardiovascular function, but their effects on cardiac repolarization have not been elucidated. The repolarization phase of the cardiac action potential or QT interval of the ECG is regulated largely by potassium channels such as the delayed rectifier currents HK2 and IsK.
The effects of ovariectomy (OVX) and estradiol (E2) or dihydrotestosterone (DHT) treatment were evaluated on HK2, HERG, and IsK mRNA levels, QT duration, and quinidine-induced changes in QT interval in isolated rabbit hearts. HK2 and 0.7-kilobase IsK mRNA were downregulated in cardiac ventricular tissue from OVX rabbits treated with either E2 or DHT. The QT interval was prolonged in E2- and DHT-treated animals (OVX + vehicle, 223 +/- 6 ms; OVX + DHT, 236 +/- 10 ms; and OVX + DHT, 245 +/- 6 ms; P < .05).
The association between hormone-induced changes in baseline QT interval and the mRNA level for these channels suggests that sex hormones may play a critical role in regulating cardiac repolarization. However, the changes in baseline QT and potassium channel mRNA after hormone treatment were not concordant with the changes in QT interval after the infusion of quinidine, after which E2-treated animals responded similarly to controls (18.4 +/- 4.6% and 19.3 +/- 4.6% increase in QT interval, respectively) and DHT-treated animals exhibited less QT prolongation (11.4 +/- 3.8% increase; P < .03).
已知性激素对心血管功能有直接和间接影响，但其对心脏复极化的影响尚未阐明。心脏动作电位的复极化阶段或心电图的QT间期主要由钾通道如延迟整流电流HK2和IsK调节。
评估卵巢切除术（OVX）以及雌二醇（E2）或双氢睾酮（DHT）治疗对离体兔心脏中HK2、HERG和IsK mRNA水平、QT间期以及奎尼丁诱导的QT间期变化的影响。在用E2或DHT治疗的OVX兔的心室组织中，HK2和0.7千碱基的IsK mRNA表达下调。E2和DHT治疗的动物QT间期延长（OVX + 赋形剂组，223 ± 6毫秒；OVX + DHT组，236 ± 10毫秒；以及OVX + DHT组，245 ± 6毫秒；P < 0.05）。
激素诱导的基线QT间期变化与这些通道的mRNA水平之间的关联表明，性激素可能在调节心脏复极化中起关键作用。然而，激素治疗后基线QT和钾通道mRNA的变化与输注奎尼丁后QT间期的变化不一致，其中E2治疗的动物反应与对照组相似（QT间期分别增加18.4 ± 4.6%和19.3 ± 4.6%），而DHT治疗的动物QT延长较少（增加11.4 ± 3.8%；P < 0.03）。
