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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Renal function. (a) Serum creatinine was measured from venous blood obta...
Renal function. (a) Serum creatinine was measured from venous blood obtained from the tail. The number of mice in each group was as follows: ACE.1 KO, 11; ACE.1 WT, 12; ACE.1 HZ, 14; ACE.2 KO, 30; ACE.2 WT, 50; ACE.2 HZ, 50. (b) The creatinine clearance was measured as described in Methods. The number of mice in each group was as follows: ACE.1 KO, 5; ACE.1 WT, 6; ACE.1 HZ, 6; ACE.2 KO, 30; ACE.2 WT, 21; ACE.2 HZ, 19. All data are presented as mean ± SE. ACE.1 mice have a significant elevation of serum creatinine as compared with wild-type and heterozygous mice (P < 0.01). They also have a significant reduction of creatinine clearance as compared with these same control animals (P < 0.05). In contrast, ACE.2 knockout mice have no evidence of renal failure in that their serum creatinine and creatinine clearance values were not significantly different from wild-type littermate controls. While the creatinine clearance of ACE.1 and ACE.2 heterozygous mice is somewhat elevated above the levels of wild-type mice, these differences do not reach statistical significance. The difference in serum creatinine between ACE.1 wild-type mice and ACE.2 wild-type mice is probably due to the use of different reference laboratories to obtain these data.