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

doi:10.1681/ASN.2005080833

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

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Witt, Henning
Max Planck Society;

Ruiz, Patricia
Max Planck Society;

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Pfab, T., Thöne-Reineke, C., Theilig, F., Lange, I., Witt, H., Maser-Gluth, C., et al. (2006). Diabetic endothelin B receptor–deficient rats develop severe hypertension and progressive renal failure. Journal of the American Society of Nephrology (Baltimore, MD), 17, 1082-1089. doi:10.1681/ASN.2005080833.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0010-8450-A

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.