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, an
d 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 25
4 +/- 36 mL/min and coronary blood flow by 21% +/- 2% within 2 hours. Estra
ce increased uterine blood flow from 30 +/- 7 to 260 +/- 62 mL/min and coro
nary blood flow by 8% +/- 4% within 3 hours. Raloxifene increased uterine b
lood 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 effect
s in the ovariectomized ewe. The coronary and uterine responses are partial
ly mediated by nitric oxide.