Role of endothelin ETB receptor in partial ablation-induced chronic renal failure in rats

Yuka Okada, Mariko Nakata, Hiromi Izumoto, Mai Takasu, Naoko Tazawa, Masanori Takaoka, Cheryl E. Gariepy, Masashi Yanagisawa, Yasuo Matsumura

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We investigated the role of endothelin ETB receptor in the remnant kidney model of chronic renal failure, by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the endothelin ET B receptor gene. After 5/6 nephrectomy, systolic blood pressure and renal functional parameters were measured for 12 weeks. At the end of the experimental period, arterial blood sample, remnant kidney, heart and aorta were collected and used for biochemical measurements and histopathological studies. The ETB-deficient sl/sl rats exhibited earlier and higher increases in systolic blood pressure, urinary protein excretion, blood urea nitrogen and plasma creatinine concentration, compared with cases in wild-type rats. Histopathologic examination of the kidney revealed glomerular and tubular lesions, alterations of which were more severe in sl/sl than in wild-type rats. While aortic endothelin-1 contents were increased similarly in both groups, the level of renal endothelin-1 content was significantly elevated in sl/sl rats, but not in the wild-type rats. These results suggest that enhanced endothelin-1 production is at least partly responsible for the increased susceptibility to partial ablation-induced chronic renal failure in ETB receptor-deficient rats and that ETB receptor-mediated actions are protective against vascular and renal injuries in this disease.

Original languageEnglish (US)
Pages (from-to)63-71
Number of pages9
JournalEuropean Journal of Pharmacology
Volume494
Issue number1
DOIs
StatePublished - Jun 21 2004

Keywords

  • Chronic renal failure
  • ET receptor
  • Endothelin-1
  • Hypertension
  • Renal mass reduction

ASJC Scopus subject areas

  • Pharmacology

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    Okada, Y., Nakata, M., Izumoto, H., Takasu, M., Tazawa, N., Takaoka, M., Gariepy, C. E., Yanagisawa, M., & Matsumura, Y. (2004). Role of endothelin ETB receptor in partial ablation-induced chronic renal failure in rats. European Journal of Pharmacology, 494(1), 63-71. https://doi.org/10.1016/j.ejphar.2004.04.046