ETB receptor protects the tubulointerstitium in experimental thrombotic microangiopathy

Masaomi Nangaku, Koei Yamada, Cheryl E. Gariepy, Tosmo Miyata, Reiko Inagi, Kiyoshi Kurokawa, Masashi Yanagisawa, Toshiro Fujita, Richard J. Johnson

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background. The characteristic features of thrombotic microangiopathy (TMA) include glomerular and peritubular capillary endothelial cell injury with thrombus formation and subsequent ischemic tubulointerstitial damage. The endothelin ETB receptor has been shown to mediate both endothelial cell proliferation and vasodilation, and we therefore hypothesized that blockade of this receptor might promote more severe injury in this model. Methods. TMA was induced in recently established transgenic rats that lack expression of ETB receptor in the kidney; these animals were compared to control rats with TMA both in the short-term (days 1 and 3) when acute glomerular injury was most manifest, and the long-term (day 17) when glomeruli have recovered but tubulointerstitial injury is still present. Rehal damage was assessed by histological analysis and blood urea nitrogen (BUN) measurements. Results. No difference in the TMA model was observed between rats with and without ETB receptor on days 1 or 3. At day 17, however, rats without the ETB receptor showed more severe tubulointerstitial injury compared with those with ETB receptor, which was associated with higher BUN levels. The tubulointerstitial damage was associated with a more severe loss of peritubular capillaries. Conclusions. These findings suggest that the ETB receptor may protect peritubular capillaries under the ischemic insult, and serve a defensive role in the tubulointerstitium induced by renal microvascular injury.

Original languageEnglish (US)
Pages (from-to)922-928
Number of pages7
JournalKidney international
Issue number3
StatePublished - 2002


  • Endothelin
  • Endothelium
  • Hemolytic-uremic syndrome
  • Hypoxia
  • Ischemia
  • Progressive renal disease
  • Renoprotection

ASJC Scopus subject areas

  • Nephrology


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