title: The protective effect of angiotensin converting enzyme inhibition in experimental renal fibrosis in mice is not mediated by bradykinin B2 receptor activation.
abstract: Unilateral ureteral obstruction (UUO) is an animal model of accelerated renal tubulointerstitial fibrosis. We have recently shown, using this model, that mice lacking the bradykinin B2-receptor (B2(-/-)) were more susceptible than control animals to the development of tubulointerstitial fibrosis. Angiotensin converting enzyme (ACE) inhibition slows down UUO-induced renal fibrosis. Since ACE-inhibition increases bradykinin and decreases angiotensin II concentrations we have verified if bradykinin is involved in the antifibrotic effects of ACE-inhibition using the UUO-model and B2(-/-) mice. Surprisingly, although ACE-inhibition significantly reduced renal fibrosis, no difference was observed between the degree of tubulointerstitial fibrosis, macrophage infiltration and cell proliferation between ACE-inhibitor treated B2(+/+) and B2(-/-) mice suggesting the absence of a role of the B2-receptor in the antifibrotic effects of ACE-inhibition. This was confirmed at the level of bradykinin-induced activity of enzymes involved in the degradation of the extracellular matrix. However in both mouse strains, ACE-inhibitors were more efficient than AT1 receptor antagonists.
authors.affiliation: Inserm U388, Institut Louis Bugnard, CHU Rangueil, 31052 Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.forename: Johan
authors.initials: J
authors.lastname: Duchene
authors.forename: Laurence
authors.initials: L
authors.lastname: Desmond
authors.forename: Eric
authors.initials: E
authors.lastname: Neau
authors.forename: Denis
authors.initials: D
authors.lastname: Calise
authors.forename: Serge
authors.initials: S
authors.lastname: Estaque
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Girolami
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy* / Q000201:enzymology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D003094:Collagen; D020778:Matrix Metalloproteinase 2