title: Estrogen metabolite 2-methoxyestradiol prevents hypertension in deoxycorticosterone acetate-salt rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Wensu
authors.initials: W
authors.lastname: Yuan
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Yu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Pavneet
authors.initials: P
authors.lastname: Singh
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Gui
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects; D003627:Data Interpretation, Statistical; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D004967:Estrogens / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004967:Estrogens; D003900:Desoxycorticosterone; D004958:Estradiol; D000077584:2-Methoxyestradiol