The protective effect of angiotensin converting enzyme inhibition in experimental renal fibrosis in mice is not mediated by bradykinin B2 receptor activation

Thromb Haemost. 2003 Apr;89(4):735-40.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Cell Division
  • Collagen / biosynthesis
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Fibrosis / drug therapy*
  • Fibrosis / enzymology*
  • Immunohistochemistry
  • Kidney / metabolism
  • Kidney / pathology*
  • Macrophages / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Transgenic
  • Receptor, Bradykinin B2 / metabolism*
  • Time Factors

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Receptor, Bradykinin B2
  • Collagen
  • Matrix Metalloproteinase 2