title: Effects of blockade of the renin-angiotensin system on tissue factor and plasminogen activator inhibitor-1 synthesis in human cultured monocytes.
abstract: OBJECTIVE
  To clarify the pathophysiological significance of the renin-angiotensin system (RAS) in monocytes, we examined the effect of its blockade on tissue factor and plasminogen activator inhibitor-1 (PAI-1) synthesis in human cultured monocytes.
  
  
  METHODS
  Monocytes were isolated from healthy volunteers and cultured. Tissue factor and PAI-1 antigens in culture medium and cells were measured by enzyme-linked immunosorbent assay and Western blotting, and mRNA levels were assessed by reverse-transcriptase polymerase chain reaction.
  
  
  RESULTS
  We show that the RAS is present in isolated human peripheral blood monocytes. Exogenous angiotensin II increased the levels of tissue factor antigen and mRNA in cultured monocytes, but not of PAI-1 synthesis. An angiotensin converting enzyme (ACE) inhibitor (captopril) and an angiotensin II type 1 (AT1) receptor antagonist (candesartan) decreased the levels of tissue factor protein and mRNA in cultured monocytes. These alterations were accompanied by a reduction in the levels of tumour necrosis factor-alpha protein and mRNA. The levels of PAI-1 protein were reduced by captopril, but not by candesartan. A bradykinin B2 receptor antagonist abolished the suppressive effect of captopril on PAI-1 antigen.
  
  
  CONCLUSIONS
  An ACE inhibitor and an AT1 receptor antagonist reduced tissue factor synthesis in these cells. We show different actions of these agents on PAI-1 synthesis. ACE inhibition decreased PAI-1 synthesis mediated by bradykinin production, but AT1 receptor inhibition had no effect.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Ishibashi
authors.forename: T
authors.initials: T
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Nakazato
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Ohkawara
authors.forename: T
authors.initials: T
authors.lastname: Teramoto
authors.forename: Y
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003470:Culture Media; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D013925:Thromboplastin; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C081643:candesartan