Long-term cardiovascular effects of high "osteoprotective" dose levels of 17 beta-estradiol in spontaneously hypertensive rats

The effects of estrogen replacement therapy in menopausal women are more ob vious on bones than on the cardiovascular system. The optimal estrogen dosa ge may differ in these different parts of the body. In hypertensive rats, l ow doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection. From 4 to 20 weeks of age , female spontaneously hypertensive rats (SHRs) were divided into four grou ps: without ovariectomy, under placebo or 17 beta-estradiol (10 mu g/kg/day ), and with ovariectomy under either placebo or 17 beta-estradiol (same dos age). Serial tail systolic blood pressure measurements were performed, and histomorphometry of the thoracic aorta was determined at the end of the stu dy. Under estrogen, blood pressure was unchanged, whereas the aortic wall-t o-lumen ratio was increased, particularly in the presence of ovariectomy. T he elastin to collagen ratio was significantly decreased, due both to a dec rease in elastin and an increase in collagen density, with no change in med ia thickness. The latter findings were not observed when ovariectomy was pe rformed. Independent of changes in wall stress, high-dose estrogen increase s the aortic extracellular matrix in female SHRs. This increase may be reve rsed in the presence of ovariectomy, suggesting that estrogen was not the o nly gonadal factor responsible for altered vascular structure and function.