Karanian J W, Ramwell P W
Laboratory of Membrane Biochemistry and Biophysics, Georgetown University Medical Center, Washington, DC, USA.
J Cardiovasc Pharmacol. 1996 Mar;27(3):312-9. doi: 10.1097/00005344-199603000-00002.
The effect of gender, gonadal steroids, and antiandrogen/antiestrogen-treatment on the isotonic response of isolated preparations of the left anterior descending coronary artery (LAD), left circumflex coronary artery, and renal artery and vein of sexually mature dogs was investigated. The maximum isotonic response of the coronary and renal vasculature to the thromboxane A2 (TXA2)-mimetic U46619 was significantly greater, and the EC50 value was significantly lower in males as compared with females. Moreover, similar gender differences in the contractile response of the coronary vasculature to norepinephrine were observed. Pretreatment of male dogs with the antiandrogens flutamide or cyproterone acetate reduced the maximum contractile response of the LAD to the TXA2-mimetic. Pretreatment of female dogs with testosterone resulted in an increase in both the maximum contractile response and EC50 value to U46619. Antiestrogen treatment of female dogs with tamoxifen was associated with an increase in the maximum contractile response of the LAD to U46619. Estrogen pretreatment of male dogs decreased both the maximum contractile response and the EC50 value to U46619. Therefore, there is a sex difference in LAD and LCX contractile responses to both U46619 and norepinephrine. These results suggest that smooth muscle reactivity of dog coronary artery to the TXA2-mimetic U46619 may be susceptible to regulation by both androgens and estrogens. The observed gender differences in the catecholamine response may be similarly altered by changes in the hormonal milieu.
研究了性别、性腺类固醇以及抗雄激素/抗雌激素治疗对性成熟犬左前降支冠状动脉(LAD)、左旋支冠状动脉和肾动脉及静脉分离制剂等张反应的影响。与雌性相比,雄性冠状动脉和肾血管对血栓素A2(TXA2)模拟物U46619的最大等张反应显著更大,且半数有效浓度(EC50)值显著更低。此外,观察到冠状动脉对去甲肾上腺素的收缩反应也存在类似的性别差异。用抗雄激素氟他胺或醋酸环丙孕酮预处理雄性犬,可降低LAD对TXA2模拟物的最大收缩反应。用睾酮预处理雌性犬,会导致对U46619的最大收缩反应和EC50值均增加。用他莫昔芬对雌性犬进行抗雌激素治疗,与LAD对U46619的最大收缩反应增加有关。用雌激素预处理雄性犬,可降低对U46619的最大收缩反应和EC50值。因此,LAD和左旋支冠状动脉对U46619和去甲肾上腺素的收缩反应存在性别差异。这些结果表明,犬冠状动脉平滑肌对TXA2模拟物U46619的反应性可能易受雄激素和雌激素的调节。观察到的儿茶酚胺反应中的性别差异可能会因激素环境的变化而发生类似改变。