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 ewes.


METHODS
Twelve ewes were chronically instrumented for measurement of mean arterial pressure, heart rate, cardiac output, coronary blood flow, and uterine blood flow. Sheep received 17beta-estradiol, Estrace, raloxifene, or KY Jelly vehicle on separate days.


RESULTS
17beta-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 17beta-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.
Zoma
W D
WD
Department of Obstetrics and Gynecology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0526, USA.
Baker
R S
RS
Clark
K E
KE
D000282:Administration, Intravaginal; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D013908:Thoracotomy; D014599:Uterus / Q000098:blood supply* / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D004965:Estrogen Antagonists; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester