Cole J, Ertoy D, Lin H, Sutliff R L, Ezan E, Guyene T T, Capecchi M, Corvol P, Bernstein K E
Department of Pathology, Emory University, Atlanta, Georgia, USA. Institute National de la Santé et de la Recherche Medicale Unit 36, College de France, Paris, France.
J Clin Invest. 2000 Dec;106(11):1391-8. doi: 10.1172/JCI10557.
While nephrologists often observe reduced hematocrit associated with inhibitors of angiotensin-converting enzyme (ACE), the basis for this effect is not well understood. We now report that two strains of ACE knockout mice have a normocytic anemia associated with elevated plasma erythropoietin levels. (51)Cr labeling of red cells showed that the knockout mice have a normal total blood volume but a reduced red cell mass. ACE knockout mice, which lack tissue ACE, are anemic despite having normal renal function. These mice have increased plasma levels of the peptide acetyl-SDKP, a possible stem cell suppressor. However, they also show low plasma levels of angiotensin II. Infusion of angiotensin II for 2 weeks increased hematocrit to near normal levels. These data suggest that angiotensin II facilitates erythropoiesis, a conclusion with implications for the management of chronically ill patients on inhibitors of the renin-angiotensin system.
虽然肾脏病学家经常观察到血管紧张素转换酶（ACE）抑制剂与血细胞比容降低有关，但这种效应的基础尚未完全了解。我们现在报告，两株ACE基因敲除小鼠出现了与血浆促红细胞生成素水平升高相关的正细胞性贫血。红细胞的（51）Cr标记显示，基因敲除小鼠的全血容量正常，但红细胞量减少。缺乏组织ACE的ACE基因敲除小鼠尽管肾功能正常，但仍患有贫血。这些小鼠血浆中肽乙酰-SDKP水平升高，乙酰-SDKP可能是一种干细胞抑制因子。然而，它们的血浆血管紧张素II水平也较低。输注血管紧张素II 2周可使血细胞比容升至接近正常水平。这些数据表明，血管紧张素II促进红细胞生成，这一结论对使用肾素-血管紧张素系统抑制剂的慢性病患者的管理具有重要意义。
