Lack of angiotensin II-facilitated erythropoiesis causes anemia in angiotensin-converting enzyme-deficient mice.
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.
Cole
J
J
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.
Ertoy
D
D
Lin
H
H
Sutliff
R L
RL
Ezan
E
E
Guyene
T T
TT
Capecchi
M
M
Corvol
P
P
Bernstein
K E
KE
D000740:Anemia / Q000097:blood*; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004909:Erythrocyte Indices; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006400:Hematocrit; D007668:Kidney / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D013599:Systole
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A