2-Methoxyestradiol attenuates hypertension and coronary vascular remodeling in spontaneously hypertensive rats

Abstract 

Objectives

Accumulating data provide evidence that some metabolites of 17β-estradiol are biologically active and mediate multiple effects on the cardiovascular and renal systems. We investigated the effect of 2-methoxyestradiol (an active metabolite of estradiol with non-feminizing activity) on the development of hypertension and myocardial vascular remodeling in male and female ovarectomized SHR.

Methods

Rats were divided into five groups: intact females, ovarectomized (OVX), OVX+ 2-methoxyestradiol (2ME), control males, and male+2ME. Systolic blood pressure was determined from 10 to 18 weeks. Structural changes in coronary vessels were quantified by an image analyzer. Immunoblotting of phosphorylated ERK1/2 and NADPH oxidase activity were performed on mesenteric arteries.

Results

Treatment with 2ME reduced the increase in systolic blood pressure in male and ovarectomized rats to values not different from those obtained in intact females. Myocardial arterioles and small arteries showed significant increases in wall-to-lumen ratio and perivascular fibrosis in male and ovarectomized rats when compared with intact females. NADPH oxidase activity was increased in mesenteric arteries from males and ovarectomized females as compared with intact females. Finally, the expression of phosphorilated ERK1/2 were significantly higher in mesenteric arteries from male and ovariectomized animals than in those from intact females. Those effects of ovarectomy and gender differences were totally or partially prevented by treatment with 2-methoxyestradiol.

Conclusions

These data demonstrate that 2-methoxyestradiol protects the vasculature from hypertension-induced myocardial arterial remodeling in male and ovarectomized SHR, and that might be in part related to decreased superoxide generation and ERK1/2 activation.

Keywords: 2-Methoxyestradiol, Mitogen activated protein kinases, NADPH oxidase-activity, Vascular remodeling, Spontaneously hypertensive rats