Gould A B, Goodman S, DeWolf R, Onesti G, Swartz C
J Lab Clin Med. 1980 Sep;96(3):523-34.
Evidence is presented implicating the renin-angiotensin system in the regulation of plasma erythropoietin concentration. Male and female rats were exposed to hypoxia at 0.43 atm for 8 hr. In male rats, individual erythropoietin values showed a positive correlation with renin, renin substrate, and angiotensin I after 8 hr of hypoxia. In female rats, renin was not elevated during hypoxia. However, after renin was injected subcutaneously, plasma renin values became similar to those in male rats and erythropoietin doubled. Individual erythropoietin values of the combined groups showed a positive correlation with plasma renin. A single oral dose of SQ 14225, an angiotensin I-converting enzyme inhibitor, reduced erythropoietin to undetectable levels in renin-injected female rats. Angiotensin II, in subpressor amounts, prevented the suppression of erythropoietin by SQ 14225. SQ 14225 also reduced renin substrate concentration at ambient pressure and during hypoxic exposure. The correlation coefficient between renin substrate and erythropoietin in rats given SQ 14225 to lower substrate or angiotensin II to increase substrate was 0.85; p < 0.0005. The increase in renin substrate that occurred during hypoxia in female rats given angiotensin II correlated positively with erythropoietin, r = 0.86; p < 0.0005.
有证据表明肾素 - 血管紧张素系统参与血浆促红细胞生成素浓度的调节。将雄性和雌性大鼠置于0.43个大气压的低氧环境中8小时。在雄性大鼠中，低氧8小时后，个体促红细胞生成素值与肾素、肾素底物和血管紧张素I呈正相关。在雌性大鼠中，低氧期间肾素未升高。然而，皮下注射肾素后，血浆肾素值变得与雄性大鼠相似，促红细胞生成素增加了一倍。合并组的个体促红细胞生成素值与血浆肾素呈正相关。单次口服剂量的血管紧张素I转换酶抑制剂SQ 14225可使注射肾素的雌性大鼠的促红细胞生成素降至无法检测的水平。亚升压剂量的血管紧张素II可防止SQ 14225对促红细胞生成素的抑制作用。SQ 14225还可降低常压和低氧暴露期间的肾素底物浓度。给予SQ 14225以降低底物或给予血管紧张素II以增加底物的大鼠中，肾素底物与促红细胞生成素之间的相关系数为0.85；p < 0.0005。给予血管紧张素II的雌性大鼠在低氧期间肾素底物的增加与促红细胞生成素呈正相关，r = 0.86；p < 0.0005。
