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

Item Type:Article
Title:Functional, biochemical, and molecular investigations of renal kallikrein-kinin system in diabetic rats
Creators Name:Tschoepe, C. and Reinecke, A. and Seidl, U. and Yu, M. and Gavriluk, V. and Riester, U. and Gohlke, P. and Graf, K. and Bader, M. and Hilgenfeldt, U. and Pesquero, J.B. and Ritz, E. and Unger, T.
Abstract:A reduction of renal kallikrein has been found in non-insulin-treated diabetic individuals, suggesting that an impaired renal kallikrein-kinin 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 B2 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:Bradykinin, Diabetic Nephropathies, Experimental Diabetes Mellitus, Glomerular Filtration Rate, Insulin, Kallikreins, Kidney, Kidney Cortex, Kidney Medulla, Kinins, Peptidyl-Dipeptidase A, Prekallikrein, Proteinuria, Reference Values, Animals, Rats
Source:American Journal of Physiology Heart and Circulatory Physiology
ISSN:0363-6135
Publisher:American Physiological Society (U.S.A.)
Volume:277
Number:6 Pt 2
Page Range:H2333-H2340
Date:December 1999
Official Publication:http://ajpheart.physiology.org/cgi/content/abstract/277/6/H2333
PubMed:View item in PubMed

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