EFFECTS OF A PURE ANTIESTROGEN AND PROGESTERONE ON ESTROGEN-MEDIATED ALTERATIONS OF BLOOD-FLOW AND PROGESTERONE-RECEPTOR EXPRESSION IN THE AORTA OF OVARIECTOMIZED RABBITS

There is ample evidence from epidemiological studies that estrogen-rep lacement therapy protects postmenopausal women against cardiovascular disease. One explanation for this beneficial effect could be the impro vement of blood flow under estrogen therapy. By using ultrasound and D oppler color flow mapping we demonstrated in the aorta of ovariectomiz ed rabbits a significant dose-dependent increase in blood flow after t reatment with 17 beta-estradiol. An increase in blood flow was already observed within Ih of estradiol treatment and lasted until the end of a 14-day treatment phase. Progesterone did not attenuate the effects of 17 beta-estradiol on aortic blood flow. The pure estrogen receptor antagonist ZM 182780, however, dose-dependently reversed the effect of 17 beta-estradiol on blood flow after the 14-day treatment phase, but was not able to antagonize the rapid 17 beta-estradiol effect on bloo d flow after 1 h. After killing the animals mRNA and protein expressio n of the progesterone receptor (PR), a known estrogen-responsive gene in classic target organs, were examined. Analogous to the blood flow r esults the PR mRNA level increased dose-dependently after 17 beta-estr adiol treatment, whereas ZM 182780 was able to reverse this effect. Im munohistochemical localization of PR in the aortic wall revealed an in crease in immunoreactivity in fibroblasts of the adventitia after 17 b eta-estradiol treatment. ZM 182780, and to a lesser degree progesteron e, reversed the 17 beta-estradiol-induced increase in PR immunoreactiv ity. PR immunoreactivity was further detected in endothelial and smoot h muscle cells, but the various hormonal treatments had no discernible effect on the PR mRNA level in these cellular compartments. Our findi ngs in the aorta of OVX rabbits suggest that (a) 17 beta-estradiol exh ibits a rapid effect on arterial tone, (b) the pure estrogen receptor antagonist ZM 182780 inhibits the 17 beta-estradiol effect on blood fl ow and PR mRNA and (c) progesterone does not attenuate the beneficial effect of estrogens on arterial tone. (C) 1997 Elsevier Science Ltd. A ll rights reserved.