Effect of estrogen and angiotensin-converting enzyme inhibitor on vascular remodeling in ovariectomized spontaneously hypertensive rats

Objective: The present study evaluated whether estrogen influences the effect of angiotensin-converting enzyme inhibition in preventing the vascular remodeling induced by hypertension and also investigated the signal mechanism involved in that effect. Design: Ten-week-old female spontaneously hypertensive rats were ovariectomized (OVX) and randomly assigned to the groups: untreated OVX and treated with 17 beta-estradiol (estradiol, 1.5 mg) and/or captopril (5 mg/kg/day). Evolution of systolic blood pressure was determined until 18 weeks. At that time, the heart and mesentery were excised. Structural changes in coronary vessels were quantified by an image analyzer. Inmunoblotting was performed on mesenteric arteries for determination of phosphorylated (ERK1/2). Results: Estradiol treatment enhanced the antihypertensive effect of captopril in OVX rats. Treatment with captopril slightly modified the media cross-sectional area and wall-to-lumen of myocardial arterioles from OVX spontaneously hypertensive rats, whereas coadministration of captopril and estradiol significantly reduced the media cross-sectional area, wall-to-lumen ratio, and perivascular fibrosis in OVX spontaneously hypertensive rats. Captopril alone did not significantly inhibit extracellular signal-regulated kinase 1/2 phosphorylation, whereas coadministration of captopril and estradiol significantly attenuated this parameter. Conclusions: These results indicate that estrogen may enhance the angiotensin-converting enzyme inhibition-mediated improvement of vascular remodeling in hypertension, which may be partly mediated via inhibition of extracellular signal-regulated kinase 1/2.