Coronary and uterine vascular responses to raloxifene in the sheep

Objective: We sought to determine whether raloAfene increases coronary and uterine blood flow in ovariectomized ewes. Study Design: Twelve ewes were chronically instrumented for measurement of mean arterial pressure, heart rate, cardiac output, coronary blood flow, and uterine blood flow. Sheep received 17ß-estradiol, Estrace, raloxifene, or KY Jelly vehicle on separate days. Results: 17ß-Estradiol increased uterine blood flow from 21 ± 3 to 254 ± 36 mpl/min and coronary blood flow by 21% ± 2% within 2 hours. Estrace increased uterine blood flow from 30 ± 7 to 260 ± 62 ml/min and coronary blood flow by 8% ± 4% within 3 hours. Raloxifene increased uterine blood flow from 20 ± 3 ml/min to 220 ± 53 mUmin by 6 hours and coronary blood flow by 22% ± 5% within 24 hours. To determine whether hemodynamic responses were mediated by nitric oxide, l-nitroarginine methyl ester was administered and produced an approximate 50% decrease in uterine blood flow for all 3 compounds. l-Nitroarginine methyl ester attenuated increases in coronary blood flow induced by I7ß-estradiol, Estrace, and raloxifene. Conclusions: Raloxifene has significant coronary and uterine vascular effects in the ovariectomized ewe. The coronary and uterine responses are partially mediated by nitric oxide.