title: Induction of functional bradykinin b(1)-receptors in normotensive rats and mice under chronic Angiotensin-converting enzyme inhibitor treatment.
abstract: BACKGROUND
  The physiological effects of ACE inhibitors may act in part through a kinin-dependent mechanism. We investigated the effect of chronic ACE-inhibitor treatment on functional kinin B(1)- and B(2)-receptor expression, which are the molecular entities responsible for the biological effects of kinins.
  
  
  RESULTS
  Rats were subjected to different 6-week treatments using various mixtures of the following agents: ACE inhibitor, angiotensin AT(1)-receptor antagonist, and B(1)- and B(2)-receptor antagonists. Chronic ACE inhibition induced both renal and vascular B(1)-receptor expression, whereas B(2)-receptor expression was not modified. Furthermore, with B(1)-receptor antagonists, it was shown that B(1)-receptor induction was involved in the hypotensive effect of ACE inhibition. Using microdissection, we prepared 10 different nephron segments and found ACE-inhibitor-induced expression of functional B(1)-receptors in all segments. ACE-inhibitor-induced B(1)-receptor induction involved homologous upregulation, because it was prevented by B(1)-receptor antagonist treatment. Finally, using B(2)-receptor knockout mice, we showed that ACE-inhibitor-induced B(1)-receptor expression was B(2)-receptor independent.
  
  
  CONCLUSIONS
  This study provides the first evidence that chronic ACE-inhibitor administration is associated with functional vascular and renal B(1)-receptor induction, which is involved in ACE-inhibitor-induced hypotension. The observed B(1)-receptor induction in the kidney might participate in the known renoprotective effects of ACE inhibition.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale INSERM U 388, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Marin-Castaño
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.forename: Eric
authors.initials: E
authors.lastname: Neau
authors.forename: Françoise
authors.initials: F
authors.lastname: Praddaude
authors.forename: Christiane
authors.initials: C
authors.lastname: Pecher
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Ader
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Girolami
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D015232:Dinoprostone / Q000096:biosynthesis; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism; D000077405:Irbesartan; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D017257:Ramipril / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D013995:Time
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D065168:Bradykinin Receptor Antagonists; C120984:R 715; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D013777:Tetrazoles; C065679:icatibant; D000077405:Irbesartan; D015232:Dinoprostone; D017257:Ramipril; D001920:Bradykinin