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Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation
Author(s) -
Chisi John E.,
Briscoe Cecilia V.,
Ezan Eric,
Genet Roger,
Riches Andrew C.,
WdzieczakBakala Joanna
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02073.x
Subject(s) - captopril , haematopoiesis , in vivo , bone marrow , pharmacology , chemistry , cell growth , stem cell , biology , medicine , endocrinology , immunology , biochemistry , microbiology and biotechnology , blood pressure
Angiotensin I‐converting enzyme (ACE) has been shown to be involved in the catabolism of the tetrapeptide acetyl‐Ser–Asp–Lys–Pro (AcSDKP). As AcSDKP is a physiological inhibitor of haematopoietic stem cell proliferation, we investigated the in vitro and in vivo effects of captopril, one of the specific inhibitors of ACE, on the proliferation of primitive haematopoietic cells. Regenerating bone marrow cells obtained from mice given one injection of cytosine arabinoside (100 mg/kg) as well as SA2 myeloid leukaemia cells were incubated in vitro for 24 h with 10 −6 m captopril. Captopril significantly reduced the proportion of high proliferative potential colony‐forming cells (HPP‐CFC‐1) in S‐phase, whereas it had no effect on the proportion of SA2 leukaemic colony‐forming cells in S‐phase. When given in vivo to mice 1 h after 2 Gy γ‐irradiation or cytosine arabinoside (AraC) injection, captopril (100 mg/kg) was shown to prevent HPP‐CFC‐1 entry into S‐phase induced by these cytotoxic treatments. The observed effects correlated with a reduction in ACE degradative activity and an increase in the level of endogenous AcSDKP both in the supernatants of captopril‐treated bone marrow cells and in plasma of treated animals. The present findings suggest that AcSDKP might mediate the observed in vitro and in vivo inhibitory effects of captopril on primitive haematopoietic cell proliferation.