Functional, biochemical, and molecular investigations of renal kallikrein-kinin system in diabetic rats

Functional, biochemical, and molecular investigations of renal kallikrein-kinin system in diabetic rats

Author Tschope, C. Google Scholar
Reinecke, A. Google Scholar
Seidl, U. Google Scholar
Yu, M. Google Scholar
Gavriluk, V Google Scholar
Riester, U. Google Scholar
Gohlke, P. Google Scholar
Graf, K. Google Scholar
Bader, M. Google Scholar
Hilgenfeldt, U. Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Ritz, E. Google Scholar
Unger, T. Google Scholar
Institution Free Univ Berlin
Univ Kiel
Univ Heidelberg
Max Delbruck Ctr Mol Med
Humboldt Univ
Universidade Federal de São Paulo (UNIFESP)
Abstract A reduction of renal kallikrein has been found in non-insulin-treated diabetic individuals, suggesting that an impaired renal kallikreinkinin system (KKS) contributes to the development of diabetic nephropathy. We analyzed relevant components of the renal KKS in non-insulin-treated streptozotocin (STZ)-induced diabetic rats. Twelve weeks after a single injection of STZ, rats were normotensive and displayed hyperglycemia, polyuria, proteinuria, and reduced glomerular filtration rate. Blood bradykinin (BK) levels and prekallikrein activity were significantly increased compared with controls. Renal kallikrein activity was reduced by 70%, whereas urinary BK levels were increased up to threefold. Renal kininases were decreased as indicated by a 3-fold reduction in renal angiotensin-converting enzyme activity and a 1.8-fold reduction in renal expression of neutral endopeptidase 24.11. Renal cortical expression of kininogen and Bg receptors was enhanced to 1.4 and 1.8-fold, respectively Our data suggest that increased urinary BK levels found in severely hyperglycemic STZ-diabetic rats are related to increased filtration of components of the plasma KKS and/or renal kininogen synthesis in combination with decreased renal kinin-degrading activity. Thus, despite reduced renal kallikrein synthesis, renal KKS is activated in the advanced stage of diabetic nephropathy.
Keywords diabetic nephropathy
kininogen
neutral endopeptidase 24.11
angiotensin-converting enzyme
bradykinin B-2 receptor
streptozotocin
Language English
Date 1999-12-01
Published in American Journal Of Physiology-heart And Circulatory Physiology. Bethesda: Amer Physiological Soc, v. 277, n. 6, p. H2333-H2340, 1999.
ISSN 0363-6135 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent H2333-H2340
Origin http://ajpheart.physiology.org/content/277/6/H2333
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000084143000027
URI http://repositorio.unifesp.br/11600/42348

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