Coronary and uterine vascular responses to raloxifene in the sheep

OBJECTIVE: We sought to determine whether raloxifene increases coronary and uterine blood flow in ovariectomized awes. 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 17 beta-estradiol, Estrace, raloxifene, or KY Jelly vehicle on separate days. RESULTS: 17 beta-Estradiol increased uterine blood flow from 21 +/- 3 to 254 +/- 36 mL/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 mL/min 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 17 beta-estradiol, Estrace, and raloxifene. CONCLUSION: Raloxifene has significant coronary and uterine vascular effects in the ovariectomized ewe. The coronary and uterine responses are partially mediated by nitric oxide.