The protective effect of angiotensin converting enzyme inhibition in experimental renal fibrosis in mice is not mediated by bradykinin B2 receptor activation.
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.
Schanstra
Joost P
JP
Inserm U388, Institut Louis Bugnard, CHU Rangueil, 31052 Toulouse, France.
Duchene
Johan
J
Desmond
Laurence
L
Neau
Eric
E
Calise
Denis
D
Estaque
Serge
S
Girolami
Jean-Pierre
JP
Bascands
Jean-Loup
JL
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D003094:Collagen; D020778:Matrix Metalloproteinase 2