Background – Ovariectomized sheep are a useful model of postmenopausal osteoporosis and other postmenopausal conditions. Estrogen may have a protective effect on the coronary arteries in postmenopausal women. The effects of raloxifene, a selective estrogen receptor modulator, on coronary arteries in aged ovariectomized ewes was investigated.

Methods and Results – Forty eight aged ewes were randomly assigned to undergo sham surgery (Sham, n=7), ovariectomy (OVX, n=10), ovariectomy with estradiol supplementation (OVXE, n=8), ovariectomy with raloxifene supplementation, 0.02 mg/kg per day (RAL1, n=10), or ovariectomy with raloxifene supplementation, 0.10 mg/kg per day (RAL2, n=13). Contrast coronary angiography was performed 6 months after intervention. Diameters of the right main and left anterior descending coronary arteries in the RAL1, RAL2 and Sham groups were not different from each other, but were significantly greater than the OVX and OVXE groups. Intracoronary nitroglycerin did not affect the relationships of the diameters in any group. There were no differences in vascular remodeling between the groups.

Conclusions – The results indicate that raloxifene in this sheep model allows greater dilation of coronary arteries than estrogen. Raloxifene may provide a significant protective functional effect on coronary arteries in postmenopausal heart disease.