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| Item Type: | Article |
|---|---|
| Title: | Diabetic endothelin B receptor-deficient rats develop severe hypertension and progressive renal failure |
| Creators Name: | Pfab, T., Thoene-Reineke, C., Theilig, F., Lange, I., Witt, H., Maser-Gluth, C., Bader, M., Stasch, J.P., Ruiz, P., Bachmann, S., 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 |
| ISSN: | 1046-6673 |
| Publisher: | American Society of Nephrology |
| Volume: | 17 |
| Number: | 4 |
| 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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