Effects of long-term ovariectomy and estrogen replacement on clonidine-evoked reductions in blood pressure and hemodynamic variability

Effects of long-term ovariectomy and estrogen replacement on clonidine-evoked reductions in blood pressure and hemodynamic variability
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DOI:
10.1097/00005344-200405000-00001
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发表时间:
2004-05-01
影响因子:
3
通讯作者:
Abdel-Rahman, AA
Abdel-Rahman, AA
中科院分区:
医学4区
文献类型:
--
作者:
El-Mas, MM;Abdel-Rahman, AA

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本研究调查了 12 周卵巢切除术 (OVX) 和补充雌激素 (OVXE2) 对中枢作用抗高血压药可乐定对 Sprague-Dawley 大鼠血压、血流动力学变异性和运动活动的急性影响的影响。还评估了雌激素消耗和补充对外周介导的肼屈嗪低血压反应的影响,以确定雌激素-可乐定相互作用的选择性。无线电遥测技术用于血压和运动活动测量。采用血流动力学变异性的三个时域指数:(1)平均动脉压(SDMAP)的标准差作为血压变异性的测量,以及(2)R-R间期(SDRR)的标准差和R-R间期连续差值的均方根(rMSSD)作为心率变异性的测量。在对照(假手术)大鼠中,可乐定(30 微克/千克,腹腔注射)引起 MAP、血压变异性 (SDMAP) 和总体心率变异性 (SDRR) 显着降低。 OVX 大鼠中 MAP 及其变异指数 (SDMAP) 的降低显着增强,并在雌激素替代(17β-雌二醇皮下颗粒,14.2 杯/天,12 周)后恢复至假手术水平。可乐定仅在 OVX 大鼠中降低运动活性。与可乐定相反,肼屈嗪(0.5 mg/kg,腹腔注射)的低血压并未因 OVX 或雌激素替代疗法而改变。这些发现表明,雌激素对中枢性低血压有负调节作用,而对外周源性低血压则没有影响。此外,结果表明心血管自主控制与 OVX 大鼠对可乐定降血压反应的增强有关。
The present study investigated the influence of 12-week ovariectomy (OVX) and estrogen supplementation (OVXE2) on the acute effects of the centrally acting antihypertensive agent clonidine on blood pressure, hemodynamic variability, and locomotor activity in Sprague-Dawley rats. The effects of estrogen depletion and repletion on the peripherally mediated hypotensive response to hydralazine were also evaluated to determine the selectivity of estrogen-clonidine interaction. The radiotelemetry technique was used for blood pressure and locomotor activity measurements. Three time-domain indices of hemodynamic variability were employed: (1) the standard deviation of mean arterial pressure (SDMAP) as a measure of blood pressure variability, and (2) the standard deviation of R-R intervals (SDRR) and the root mean square of successive differences in R-R intervals (rMSSD) as measures of heart rate variability. In control (sham-operated) rats, clonidine (30 mug/kg, i.p.) elicited significant decreases in MAP, blood pressure variability (SDMAP), and overall heart rate variability (SDRR). The reductions in MAP and its variability index (SDMAP) were significantly augmented in OVX rats and restored to sham-operated levels after estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 mug/d, 12 weeks). The locomotor activity was reduced by clonidine only in OVX rats. In contrast to clonidine, hydralazine (0.5 mg/kg, i.p.) hypotension was not altered by OVX or estrogen replacement. These findings suggest that estrogen negatively modulates centrally evoked hypotension versus no effect on hypotension of peripheral origin. Further, the results implicate the cardiovascular autonomic control in the enhanced hypotensive response to clonidine in OVX rats.