Estrogen Metabolite 2-methoxyestradiol Prevents Hypertension in Deoxycorticosterone Acetate-salt Rats

Purpose

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.

Methods

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.

Results

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.

Conclusions

2ME treatment prevents the development of hypertension in DOCA-salt rats, implicating a therapeutic potential of 2ME in hypertension treatment.