Hemodynamic response to tibolone in reproductive and nonreproductive tissues in the sheep

OBJECTIVE: We sought to determine the hemodynamic effects of tibolone in re productive and nonreproductive tissues in the nonpregnant ovariectomized sh eep. STUDY DESIGN: Six ewes were chronically instrumented for measurement of mea n arterial pressure, heart rate, cardiac output, and coronary and uterine b lood flow. A dose response curve was generated for intravenous tibolone (1. 25, 2.5, and 5 mg) and compared with intravenous 17 beta -estradiol (1 mug/ kg body weight). To determine whether tibolone-related cardiovascular respo nses 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 este r. RESULTS: Tibolone significantly increased coronary blood flow in a dose-rel ated 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 significan tly 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 meth yl ester attenuated tibolone-induced increases in uterine blood flow by 84% +/- 4% and abolished the increase in coronary blood flow. ICI 182,780 inhi bited all tibolone-induced cardiovascular responses. CONCLUSION: Tibolone significantly increases coronary and uterine blood flo w in ovariectomized ewes. The coronary and uterine vascular responses are m ediated via an estrogen receptor-dependent mechanism and are produced mainl y by nitric oxide.