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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 2006

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Endothelin B Receptors
Diabetic Nephropathies
Renal Insufficiency
Hypertension
Kidney
Albuminuria
Endothelins
Endothelin-1
Renin-Angiotensin System
Streptozocin
Renin
Creatinine
Nitric Oxide
Sodium
Diet

ASJC Scopus subject areas

  • Nephrology

Cite this

Pfab, T., Thöne-Reineke, C., Theilig, F., Lange, I., Witt, H., Maser-Gluth, C., ... 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

Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure. / Pfab, Thiemo; Thöne-Reineke, Christa; Theilig, Franziska; Lange, Ines; Witt, Henning; Maser-Gluth, Christiane; Bader, Michael; Stasch, Johannes Peter; Ruiz, Patricia; Bachmann, Sebastian; Yanagisawa, Masashi; Hocher, Berthold.

In: Journal of the American Society of Nephrology, Vol. 17, No. 4, 04.2006, p. 1082-1089.

Research output: Contribution to journalArticle

Pfab, T, Thöne-Reineke, C, Theilig, F, Lange, I, Witt, H, Maser-Gluth, C, Bader, M, Stasch, JP, 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, vol. 17, no. 4, pp. 1082-1089. https://doi.org/10.1681/ASN.2005080833
Pfab, Thiemo ; Thöne-Reineke, Christa ; Theilig, Franziska ; Lange, Ines ; Witt, Henning ; Maser-Gluth, Christiane ; Bader, Michael ; Stasch, Johannes Peter ; Ruiz, Patricia ; Bachmann, Sebastian ; Yanagisawa, Masashi ; Hocher, Berthold. / Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure. In: Journal of the American Society of Nephrology. 2006 ; Vol. 17, No. 4. pp. 1082-1089.
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