Study The Effect Of Losartan On Haematopoietic Progenitor Advantaged Differentiation And Proliferation

Objective To investigate the effect and molecular mechanism of losartan, an AT1-specific antagonist, on the advantaged differentiation of haematopoietic progenitors. And the relationship between the effect of losartan and its concentrations was explored.Methods Cord blood from normal full term uterine incision delivery fetus was used. Mononuclear cells was separated and purified by lymphoid separating medium , then added to suspension medium and cultured with the losartan of different concentrations. After incubation, cells were transferred to methylcellulose semisolid medium and cultured fourteen days. The numbers of colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) colonies were counted . Flowcytometry was used to detect the proportion of erythroid and myeloid. Nested RT-PCR was used to determine the expression of angiotensinâ…¡type 1 receptor (AT1R).Resultsâ‘ AT1R mRNA was detectable at day 6 and 9. This expression was blocked by losartan, an AT1-specific antagonist.â‘¡The number of BFU-E colonies was inhibited by losartan while the number of CFU-GM was promoted by it. Those effects were dose-dependent. The regression equations were Y=100.125-22.496 lgx(X:losartan;Y:number of BFU-E colonies)and Y=220.594+21.882 lgx(X:losartan;Y:number of CFU-GM colonies).â‘¢Losartan could inhibit the proliferation of erythroid and promote the myeloid. The regression equations were Y=4296.032-435.335 lgx(X:losartan;Y:number of erythroid)and Y=5430.975+643.853 lgx(X:losartan;Y:number of myeloid).â‘£The effects of losartan were maximal at the concentration of 20 nM/ml.Conclusion Through blocking the binding of angiotensinâ…¡and AT1R, losartan inhibits the proliferation of erythroid progenitors while promotes that of myeloid. Those effects are dose-dependent. The maximal concentration of losartan is 20 nM/ml.