K. Shindo et al., CAPTOPRIL INHIBITS NEUTROPHIL SYNTHESIS OF LEUKOTRIENE B-4 IN-VITRO AND IN-VIVO, The Journal of immunology, 153(12), 1994, pp. 5750-5759
The aim of this investigation was to determine the effects of metallop
roteinase inhibitors on leukotriene (LT) A(4) hydrolase in human neutr
ophil cytosol and to examine the effects of captopril on intact neutro
phils in vitro and in vivo. Cytosolic fractions were assayed for LTA(4
) hydrolase and 5-lipoxygenase activity in the presence or absence of
inhibitors. Only bestatin, 1,10-O-phenanthroline, captopril and fosino
prilat demonstrated significant effects. The IC50 of captopril and fos
inoprilat for LTA(4) hydrolase activity were 500 mu M and 1 mM, respec
tively. No inhibition of 5-lipoxygenase activity in cytosolic fraction
s was detected. The effect of captopril was only minimally reversed by
ZnSO4. The IC50 of captopril for inhibition of LTB(4) synthesis in in
tact neutrophils was 63 mu M. Furthermore, 5-HETE production in intact
cells was diminished 25.3 +/- 8.5% in the presence of 1 mM captopril.
Oral captopril inhibited stimulated LTB(4) release by subsequently is
olated neutrophils by 48.1 +/- 5.6% and 5-HETE release by 43.2 +/- 5.5
%. Thus, captopril is an inhibitor of LTB(4) synthesis in neutrophils
in vitro and in vivo. However, there are differences between the poten
cy of this drug as assessed in cytosol and intact cell studies. This s
tudy significantly extends previous reports in that it demonstrates th
at captopril is a more potent inhibitor of LTB(4) synthesis in intact
neutrophils than in cytosol and in that it demonstrates an inhibitory
effect of captopril on synthesis of LTB(4) by neutrophils exposed to c
aptopril in vivo.