Lack of angiotensin II–facilitated erythropoiesis causes anemia in angiotensin-converting enzyme–deficient mice
Justin Cole, … , Pierre Corvol, Kenneth E. Bernstein
Justin Cole, … , Pierre Corvol, Kenneth E. Bernstein
Published December 1, 2000
Citation Information: J Clin Invest. 2000;106(11):1391-1398. https://doi.org/10.1172/JCI10557.
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Lack of angiotensin II–facilitated erythropoiesis causes anemia in angiotensin-converting enzyme–deficient mice

Abstract

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. 51Cr 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.

Authors

Justin Cole, Dilek Ertoy, Hsinchen Lin, Roy L. Sutliff, Eric Ezan, Tham T. Guyene, Mario Capecchi, Pierre Corvol, Kenneth E. Bernstein

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Plasma erythropoietin. Anesthetized mice were bled by cardiac puncture a...
Plasma erythropoietin. Anesthetized mice were bled by cardiac puncture and plasma was immediately frozen. Erythropoietin levels were determined by radioimmunoassay. The number of mice in each group was as follows: ACE.1 KO, 10; ACE.1 WT, 9; ACE.1 HZ, 12; ACE.2 KO, 8; ACE.2 WT, 13; ACE.2 HZ, 9. The P value comparing ACE.1 knockout mice with wild-type mice is less than 0.01. A similar comparison of ACE.2 knockout mice with wild-type gave P < 0.05. Thus, the anemia present in ACE.1 and ACE.2 knockout mice was associated with elevated plasma levels of erythropoietin. Data are presented as mean ± SE.