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Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure

Item Type:Article
Title:Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure
Creators Name:Pfab, T. and Thoene-Reineke, C. and Theilig, F. and Lange, I. and Witt, H. and Maser-Gluth, C. and Bader, M. and Stasch, J.P. and Ruiz, P. and Bachmann, S. and Yanagisawa, M. and Hocher, B.
Abstract:The endothelin (ET) system has been implicated in the pathogenesis of diabetic nephropathy. The role of the ET-B receptor(ETBR) is still unclear. The effect of ETBR deficiency on the progression of diabetic nephropathy in a streptozotocin model was analyzed in four groups: (1) Homozygous ETBR-deficient (ETBRd) diabetic rats, (2) ETBRd rats, (3) diabetic controls, and (4) wild-type controls. BP and kidney function were measured for 10 wk, followed by biochemical and histologic analysis of the kidneys. The study demonstrates that ETBRd diabetic rats on a normal-sodium diet develop severe hypertension, albuminuria, and a mild reduction of creatinine clearance. The strong BP rise seems not to be caused by activation of the renin-angiotensin-aldosterone system or by suppression of the nitric oxide system. Elevated plasma ET-1, possibly reflecting a reduced ETBR-dependent clearance, seems to cause the severe hypertension via the ETA receptor. The results do not support the hypothesis that a reduction of ETBR activity inhibits the progression of diabetic nephropathy. The study demonstrates for the first time that the combination of diabetes and ETBR deficiency causes severe low-renin hypertension with progressive renal failure.
Keywords:Animal Disease Models, Blood Pressure, Chronic Kidney Failure, Creatinine, Diabetic Nephropathies, Endothelin A Receptor, Endothelin B Receptor, Endothelin-1, Experimental Diabetes Mellitus, Hypertension, Kidney, Myocardium, Animals, Rats
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology (U.S.A.)
Page Range:1082-1089
Date:April 2006
Official Publication:https://doi.org/10.1681/ASN.2005080833
PubMed:View item in PubMed

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