Hemodynamic response to tibolone in reproductive and nonreproductive tissues in the sheep.
OBJECTIVE
We sought to determine the hemodynamic effects of tibolone in reproductive and nonreproductive tissues in the nonpregnant ovariectomized sheep.


METHODS
Six ewes were chronically instrumented for measurement of mean arterial pressure, heart rate, cardiac output, and coronary and uterine blood flow. A dose response curve was generated for intravenous tibolone (1.25, 2.5, and 5 mg) and compared with intravenous 17beta-estradiol (1 microg/kg body weight). To determine whether tibolone-related cardiovascular responses were estrogen receptor mediated and produced by nitric oxide, animals were treated on separate days with either estrogen receptor antagonist ICI 182,780 or the nitric oxide synthase inhibitor, L -nitroarginine methyl ester.


RESULTS
Tibolone significantly increased coronary blood flow in a dose-related fashion by 5% +/- 3%, 9% +/- 2%, and 11% +/- 2% for the 1.25, 2.5, and 5 mg doses, respectively. Uterine blood flow was also increased significantly in a dose-dependent manner by 98 +/- 15, 216 +/- 59, and 303 +/- 56 mL/min, for the 1.25, 2.5, and 5 mg doses, respectively. L -Nitroarginine methyl ester attenuated tibolone-induced increases in uterine blood flow by 84% +/- 4% and abolished the increase in coronary blood flow. ICI 182,780 inhibited all tibolone-induced cardiovascular responses.


CONCLUSIONS
Tibolone significantly increases coronary and uterine blood flow in ovariectomized ewes. The coronary and uterine vascular responses are mediated via an estrogen receptor-dependent mechanism and are produced mainly by nitric oxide.
Zoma
W
W
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526, USA.
Baker
R S
RS
Lang
U
U
Clark
K E
KE
D045930:Anabolic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009652:Norpregnenes / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D014599:Uterus / Q000098:blood supply
D045930:Anabolic Agents; D004791:Enzyme Inhibitors; D009652:Norpregnenes; D004958:Estradiol; D019001:Nitric Oxide Synthase; C027385:tibolone; D019331:NG-Nitroarginine Methyl Ester