Takahashi H, Ashizawa H, Takeda K U, Yoneda S, Yoshimura M, Ijichi H
J Pharmacol Exp Ther. 1982 Sep;222(3):726-30.
Central effects of sex steroids on cardiovascular regulation and on behavior were investigated by injecting conjugated estrogens i.c.v. in conscious or anesthetized rats. Conjugated estrogens (0.1-10 micrograms) produced dose-related increases in pressure and behavioral excitation in all rats and drinking in some rats. Marked increases ii pressure and excitation with tonic convulsions resulting in death were produced by similar injections of conjugated estrogens (100 micrograms). Pretreatment with angiotensin I converting enzyme inhibitor or angiotensin II analog abolished both vasopressor responses and behavioral excitation in conscious rats. When rats were later anesthetized with urethane to allow recording of sympathetic nerve activity, 10 and 100 micrograms of conjugated estrogens produced dose-related vasopressor responses accompanied by corresponding increases in peripheral sympathetic nerve activity. Again, converting enzyme inhibitor or angiotensin II analog abolished the increases in both blood pressure and sympathetic nerve activity. By contrast, when conjugated estrogens were injected i.v. up to 2 mg/kg, neither blood pressure nor sympathetic outflow was affected. Collectively, our results suggest that conjugated estrogens infused centrally activate a renin-angiotensin system in the brain, which results in sympathetic hyperactivity leading to blood pressure elevation.
通过向清醒或麻醉的大鼠脑室内注射结合雌激素，研究了性类固醇对心血管调节和行为的中枢作用。结合雌激素（0.1 - 10微克）在所有大鼠中均产生与剂量相关的血压升高和行为兴奋，在一些大鼠中还引起饮水增加。类似注射100微克结合雌激素会导致血压和兴奋显著增加，并伴有强直性惊厥，最终导致死亡。用血管紧张素I转换酶抑制剂或血管紧张素II类似物预处理可消除清醒大鼠的升压反应和行为兴奋。当大鼠随后用乌拉坦麻醉以记录交感神经活动时，10和100微克结合雌激素产生与剂量相关的升压反应，并伴有外周交感神经活动相应增加。同样，转换酶抑制剂或血管紧张素II类似物可消除血压和交感神经活动的增加。相比之下，当静脉注射高达2毫克/千克的结合雌激素时，血压和交感神经输出均未受影响。总体而言，我们的结果表明，脑室内注入的结合雌激素激活了脑中的肾素 - 血管紧张素系统，导致交感神经活动亢进，进而引起血压升高。
