ET(B) receptor protects the tubulointerstitium in experimental thrombotic microangiopathy.
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 ET(B) 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 ET(B) 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. Renal 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 ET(B) receptor on days 1 or 3. At day 17, however, rats without the ET(B) receptor showed more severe tubulointerstitial injury compared with those with ET(B) 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 ET(B) receptor may protect peritubular capillaries under the ischemic insult, and serve a defensive role in the tubulointerstitium induced by renal microvascular injury.
Nangaku
Masaomi
M
Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. mnangaku-tky@umin.ac.jp
Yamada
Koei
K
Gariepy
Cheryl E
CE
Miyata
Toshio
T
Inagi
Reiko
R
Kurokawa
Kiyoshi
K
Yanagisawa
Masashi
M
Fujita
Toshiro
T
Johnson
Richard J
RJ
D000818:Animals; D030801:Animals, Genetically Modified; D000906:Antibodies / Q000378:metabolism; D001323:Autoantibodies; D001794:Blood Pressure; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D006463:Hemolytic-Uremic Syndrome / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics* / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*
D000906:Antibodies; D001323:Autoantibodies; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C051951:antiglomerular basement membrane antibody