RESUMEN
OBJECTIVE: We sought to determine the hemodynamic effects of tibolone in reproductive and nonreproductive tissues in the nonpregnant ovariectomized sheep. STUDY DESIGN: 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. CONCLUSION: 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.
Asunto(s)
Hemodinámica/efectos de los fármacos , Norpregnenos/farmacología , Anabolizantes/administración & dosificación , Anabolizantes/farmacología , Animales , Gasto Cardíaco/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Estradiol/administración & dosificación , Estradiol/farmacología , Terapia de Reemplazo de Estrógeno , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Cinética , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Norpregnenos/administración & dosificación , Ovinos , Útero/irrigación sanguíneaRESUMEN
OBJECTIVE: We sought to determine whether raloxifene increases coronary and uterine blood flow in ovariectomized ewes. 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 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. CONCLUSION: Raloxifene has significant coronary and uterine vascular effects in the ovariectomized ewe. The coronary and uterine responses are partially mediated by nitric oxide.