Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient mice

While nephrologists often observe reduced hematocrit associated with inhibi tors of angiotensin-converting enzyme (ACE), the basis for this effect is n ot well understood. We now report that two strains of ACE knockout mice hav e a normocytic anemia associated with elevated plasma erythropoietin levels . Cr-51 labeling of red cells showed that the knockout mice have a normal t otal blood volume but a reduced red cell mass. ACE knockout mice, which lac k tissue ACE, are anemic despite having normal renal function. These mice h ave increased plasma levels of the peptide acetyl-SDKP, a possible stem cel l 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 patien ts on inhibitors of the renin-angiotensin system.