Angiotensin (Ang)-(1-7)/Mas receptor (MasR) pathway accelerates vascular repair in ischemic conditions partly by stimulating the mobilization of vascular reparative bone marrow progenitor cells (BMPCs) into blood circulation. This study tested if the endogenous MasR expression is required for the mobilization of BMPCs in response to ischemic injury. Hind limb ischemia (HLI) was induced in wild type (WT) or MasR knock out mice (MasR-KO) (in C57Bl/6J background). BMPCs in the blood circulation were quantitated by flow cytometric enumeration of Lineage
-
, Sca-1
+
and cKit
+
(LSK) cells in peripheral blood or by colony forming unit (CFU) assay. Subcutaneous osmotic pumps were used for continuous infusion of Ang-(1-7) at the rate of 1 μg/kg/min for four weeks. In vitro migration of LSK cells in response to hypoxia-regulated factors, stromal-derived factor (SDF) or by vascular endothelial growth factor (VEGF) were determined. In WT mice, HLI stimulated mobilization of LSK cells that reached maximum by day 2 (110±11 cells/mL blood, n=6). Ang-(1-7)-treatment potentiated the peak mobilization (206±24 cells/mL blood, n=8, P<0.01 compared to the untreated). MasR-KO mice have reduced number of circulating LSKs (12±3 vs 43±9 per mL blood in WT, P<0.01, n=5) (CFUs/mL blood 28±5 vs 54±8 in WT, P<0.05, n=5). In MasR-KO mice, HLI did not induce mobilization, and blood flow recovery post-HLI was lower compared to WT (52±4% vs 89±6% in WT, P<0.001, n=5), both of which were not improved by treatment with Ang-(1-7). Number of bone marrow-resident LSK cells was higher in MasR-KO mice compared to WT. Migration induced by SDF (84±6% vs 160±8% in WT, P<0.001, n=5) or VEGF (97±4% vs 146±5% in WT, P<0.001, n=4) was decreased in MasR-KO. These results suggest that MasR deficiency causes impaired mobilization of BMPCs likely by decreasing their sensitivity to hypoxia-regulated factors. Therefore endogenous MasR expression is essential for ischemia-dependent mobilization of BMPCs.