Bradykinin B2 receptors as a target in diabetic nephropathy.
Diabetic nephropathy is the leading cause of chronic renal failure in countries in the western world. Human polymorphism studies have suggested a nephroprotective effect that is mediated by bradykinin B2 receptors. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers have an additive nephroprotective effect in patients with diabetes, which may be due to ACE-inhibitor-mediated increases in the levels of bradykinin. There is also evidence from studies conducted in genetically altered mice to suggest that bradykinin is nephroprotective. Finally, evidence from animal models of nephropathy indicates that some of the beneficial effects of ACE inhibitors and vasopeptidase inhibitors are due to the action of bradykinin at B2 receptors. These data establish that stimulation of bradykinin B2 receptors is a target in diabetic nephropathy, and should provide impetus for the development of non-peptide, selective bradykinin B2 agonists.
Doggrell
Sheila A
SA
Division of Health Practice, Auckland University of Technology-Akoranga Campus, Auckland, New Zealand. s.doggrell@xtra.co.nz
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D011355:Prodrugs / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000378:metabolism*
C479877:AVE 7688; D000806:Angiotensin-Converting Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D011355:Prodrugs; D011480:Protease Inhibitors; D043782:Receptor, Bradykinin B2; D000804:Angiotensin II