Abstract 10776: Role of the NH2-terminal Active Domain of Angiotensin-I Converting Enzyme on the Erythropoietic Adaptations Induced by Aerobic Exercise Training
Exercise training (ET) stimulates the erythropoietic system as it increases the number of circulating hematopoietic stem cells (HSC), the percentage of circulating reticulocytes (Ret) and reduces erythrocyte lifespan (Erylifespan). The renin-angiotensin system (RAS) exerts effects on erythropoiesis by inactivating the negative hemoregulador tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) by the NH2-terminal active domain of the angiotensin-I converting enzyme (ACE). This work investigated the role played by the NH2-terminal active domain of ACE in the ET-induced erythropoietic stimulation. The effect of ET (8 weeks of swimming training 60 min/d, 5d/week, followed by an increase in daily training frequency in week 9 to 2 times and in week 10 to 3 times) and captopril treatment (Cap, 10 mg.kg-1.d-1) on BP, HR, exercise tolerance and skeletal muscle biochemistry was studied in normotensive female Wistar rats divided in 4 groups: control (C, n=16), control with Cap (C-Cap, n=16), trained (T, n=14) and trained with Cap (T-Cap, n=14). BP was not affected by the ET or Cap in any group but the ET reduced resting HR, increased exercise tolerance and skeletal muscle citrate synthase activity in trained groups. Plasma ACE NH2-terminal active domain activity was increased 60% in T and which was completely inhibited in T-Cap. The ET increased ANG II levels by 20% in both training groups. Ac-SDKP levels were drastically reduced in T to 20% of C levels and Cap increased Ac-SDKP levels by 150% in C-Cap and by 200% in T-Cap. The number of CD34+/CD45dim HSC quantified by fluorescence-activated cell sorter analysis was enhanced 200 and 100% in the circulation and bone marrow, respectively, in the T group and in T-Cap it was increased 40 and 30% in the circulation and bone marrow (BM), respectively. The functional assay by burst forming unit-erythroid showed a 3-fold increase in both the BM and the circulation in T group which was blunted in the T-Cap group. Ret was increased in T group by 300% and by 100% in T-Cap group. Erylifespan decreased 50% in T and 20% in T-Cap. These findings show that ET-induced erythropoietic stimulation is at least partially related to the increase in the activity of the ACE NH2-terminal active domain which reduces the Ac-SDKP levels.
- © 2011 by American Heart Association, Inc.