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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

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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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Figure 6

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Red cell mass. Whole blood was obtained by cardiac puncture from donor A...
Red cell mass. Whole blood was obtained by cardiac puncture from donor ACE.2 heterozygous mice. After labeling with 51Cr, an aliquot was infused via a carotid artery catheter. After allowing for equilibration, blood was obtained by cardiac puncture and used to determine total blood volume and total red cell volume. An implied plasma volume was then calculated. All data were normalized for the weight of the animal. The number of mice in each group was as follows: ACE.2 KO, 7; ACE.2 WT, 7. While the blood volume of ACE.2 knockout mice is equivalent to that of wild-type mice, the data show that the ACE.2 knockout mice have roughly a 25% reduction of red cell mass (P < 0.01). Data are presented as mean ± SE.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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