Does endothelin B receptor deficiency ameliorate the induction of peritoneal fibrosis in experimental peritoneal dialysis?
BACKGROUND
Peritoneal fibrosis is a serious complication of peritoneal dialysis (PD); however, the mechanisms are poorly understood. The endothelin system exhibits potent pro-fibrotic properties and is known to be stimulated in peritoneal fibrosis. Thus, our study aimed at elucidating the impact of the endothelin B (ETB) receptor on peritoneal membrane thickening by means of an ETB-deficient rat model (ETB(-)(/)(-)) in experimental PD.


METHODS
Wild-type (WT) and ETB(-/-) rats were randomly allocated to four groups (each group n = 10): (i) WT Sham, (ii) WT PD, (iii) ETB(-/-) Sham and (iv) ETB(-/-) PD. All animals underwent surgical implantation of a port for intraperitoneal administration and 1 week of habituation to the procedure by administration of 2 ml of saline once daily. Afterwards, all animals were switched to 12 weeks of 15 ml of saline (Sham groups) or commercially available PD fluid containing 3.86% glucose (PD groups) administered twice daily. Afterwards, animals were sacrificed, and samples from visceral as well as parietal peritoneum were obtained. The samples were stained with Sirius-Red, and at 10 different sites per sample, peritoneal membrane thickness was measured using computer-aided histomorphometry devices.


RESULTS
Mean peritoneal membrane thickness was increased by PD in both WT and ETB(-/-) rats versus respective Sham controls (WT Sham: 22.3 +/- 0.7 microm/ETB Sham: 22.3 +/- 0.9 microm versus WT PD: 26.5 +/- 1.5 microm/ETB PD: 28.7 +/- 1.2 microm; P < 0.05, respectively). However, no difference in peritoneal membrane thickness was detected between WT PD and ETB(-/-) PD groups.


CONCLUSIONS
Our study demonstrates that PD increases peritoneal membrane thickness in a rat model, but deficiency of the ETB receptor has no detectable impact on this process.
Kalk
Philipp
P
Department of Pharmacology and Toxicology, Center for Cardiovascular Research, Charite, Berlin, Germany.
Rückert
Matthias
M
Godes
Michael
M
von Websky
Karoline
K
Relle
Katharina
K
Neumayer
Hans-Hellmut
HH
Hocher
Berthold
B
Morgera
Stanislao
S
D000818:Animals; D005355:Fibrosis; D023421:Models, Animal; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B / Q000502:physiology*
D044023:Receptor, Endothelin B