title: Renin inhibitors inhibited the activity of recombinant human renin but not activity in healthy human plasma.
abstract: BACKGROUND
  Activity of renin substrate cleavage (renin-like activity) was measured in vitro in plasma samples obtained from healthy human volunteers.
  
  
  METHODS
  Renin-like activity was determined using FRET (Fluorescence Resonance Energy Transfer) human renin substrate. Recombinant human renin and human plasma showed dose-dependent cleavage activity of FRET human renin substrate.
  
  
  RESULTS
  Activity of recombinant human renin was completely inhibited by either a peptidergic or a non-peptidergic renin inhibitor. However, renin-like activity in human plasma was not inhibited by these renin inhibitors. In a mixture of recombinant renin and human plasma, renin inhibitors inhibited only that part of the activity caused by recombinant renin, while the activity in plasma still remained. Human plasma did not show cleavage activity of rat FRET renin substrate. Native human prorenin showed cleavage activity of human renin substrate. This activety was also completely inhibited by renin inhibitors. Immunoprecipitation with anti-renin or anti-prorenin antibodies did not reduce the activity in human plasma. Renin-like activity in human plasma was abolished by degeneration of protein when sample was heated to 95 degrees C. Activity of both recombinant renin and human plasma was significantly inhibited by a protease inhibitor cocktail.
  
  
  CONCLUSIONS
  These results suggest that the activity of renin substrate cleavage in human plasma is not mainly caused by the renin or prorenin molecule, but probably by other proteases.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Tohon, Ehime, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Izumi
authors.initials: I
authors.lastname: Senba
authors.forename: Harumi
authors.initials: H
authors.lastname: Kanno
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Nakaoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Inaba
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000328:Adult; D000577:Amides / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D012083:Renin / Q000097:blood* / Q000378:metabolism; D055815:Young Adult; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000808:Angiotensinogen; D004792:Enzyme Precursors; D005650:Fumarates; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren; C027509:renin inhibitory peptide