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

Thiemo Pfab, Christa Thöne-Reineke, Franziska Theilig, Ines Lange, Henning Witt, Christiane Maser-Gluth, Michael Bader, Johannes Peter Stasch, Patricia Ruiz, Sebastian Bachmann, Masashi Yanagisawa, Berthold Hocher

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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.

Original languageEnglish (US)
Pages (from-to)1082-1089
Number of pages8
JournalJournal of the American Society of Nephrology
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2006

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ASJC Scopus subject areas

  • Nephrology

Cite this

Pfab, T., Thöne-Reineke, C., Theilig, F., Lange, I., Witt, H., Maser-Gluth, C., Bader, M., Stasch, J. P., Ruiz, P., Bachmann, S., Yanagisawa, M., & Hocher, B. (2006). Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure. Journal of the American Society of Nephrology, 17(4), 1082-1089. https://doi.org/10.1681/ASN.2005080833