Department of Biochemistry and Molecular Biology, Nankai University School of Medicine, Tianjin, China.
Cardiovasc Drugs Ther. 2013 Feb;27(1):17-22. doi: 10.1007/s10557-012-6428-7.
Our early work showed that the estrogen metabolite 2-methoxyestradiol (2ME) inhibits proliferation of vascular smooth muscle cells (SMCs) and vascular contractility through an endothelium-dependent mechanism. The aim of this study was to examine whether 2ME prevents the development of hypertension in rats.
A hypertensive model was established in uninephrectomized rats using deoxycorticosterone acetate (DOCA)-salt. Blood pressure in response to 2ME (treatment up to 10 weeks or single bolus) was monitored.
Our results showed that systolic blood pressure, as measured by tail-cuff plethysmography, was significantly increased in conscious rats treated with DOCA-salt for 3-10 weeks. Co-treatment with 2ME (100-300 μg/kg), but not dimethyl sulfoxide (DMSO), completely prevented the increase in blood pressure of DOCA-salt rats. After 10-week treatment, the mean arterial blood pressure (MABP) of anesthetized rats measured using PowerLab Data Acquisition System was: 84 ± 16 mmHg in normotensive control rats and 150 ± 9 mmHg in DOCA-salt rats, which was similar to that of DMSO-treated rats. Treatment with 2ME at low or high doses reduced MABP of DOCA-salt rats close to that of control normotensive rats. In addition, MABP of hypertensive DOCA-salt rats was significantly reduced in response to a single injection of 2ME. Delayed administration of 2ME reduced the further increase of blood pressure in DOCA-salt rats. However, inhibition of 2ME production by entacapone did not significantly affect blood pressure in either control or DOCA-salt rats.
2ME treatment prevents the development of hypertension in DOCA-salt rats, implicating a therapeutic potential of 2ME in hypertension treatment.
我们的早期工作表明，雌激素代谢产物 2-甲氧基雌二醇（2ME）通过内皮依赖性机制抑制血管平滑肌细胞（SMC）增殖和血管收缩性。本研究旨在探讨 2ME 是否可预防去氧皮质酮-醋酸盐（DOCA-盐）诱导的大鼠高血压的发生。
使用 DOCA-盐在单侧肾切除大鼠中建立高血压模型。通过尾套测压法监测 2ME（治疗长达 10 周或单次推注）对血压的影响。
结果显示，通过尾套测压法测量，清醒的 DOCA-盐处理大鼠的收缩压在 3-10 周内显著升高。用 2ME（100-300μg/kg）共同处理，但不用二甲亚砜（DMSO）处理，可完全预防 DOCA-盐大鼠血压升高。经过 10 周的治疗，使用 PowerLab 数据采集系统测量麻醉大鼠的平均动脉血压（MABP）为：正常血压对照组大鼠为 84±16mmHg，DOCA-盐大鼠为 150±9mmHg，与 DMSO 处理的大鼠相似。低剂量或高剂量的 2ME 处理可使 DOCA-盐大鼠的 MABP接近正常血压对照大鼠。此外，单次注射 2ME 可显著降低高血压 DOCA-盐大鼠的 MABP。延迟给予 2ME 可减少 DOCA-盐大鼠血压的进一步升高。然而，恩他卡朋抑制 2ME 的产生对正常血压或 DOCA-盐大鼠的血压均无明显影响。
2ME 治疗可预防 DOCA-盐大鼠高血压的发生，表明 2ME 在高血压治疗中具有治疗潜力。
