Effects of new peritoneal dialysis solutions, pyridoxamine and AT1 receptor blocker, on TGF-beta1 and VEGF expression in rat peritoneal mesothelial cells.
BACKGROUND
Transforming growth factor beta1 (TGF-beta1) and vascular endothelial growth factor (VEGF) are involved in peritoneal deterioration in continuous ambulatory peritoneal dialysis. The present study was designed to determine whether new peritoneal dialysis solutions (PDS), pyridoxamine (advanced glycation end products (AGE) inhibitor) or AT1 receptor blocker (ARB), affect the expression of VEGF and TGF-beta1 in rat peritoneal mesothelial cells (RPMC).


METHODS
RPMC were stimulated by phosphate-buffered saline (PBS) as control, Dianeal 1.5% (D 1.5%), Dianeal 2.5% (D 2.5%), Dianeal 4.25% (D 4.25%), Dianeal N 1.5% (N 1.5%), Dianeal N 2.5% (N 2.5%) or Extraneal (Ex). In co-incubation experiments, RPMC were stimulated with N 2.5% including pyridoxamine or olmesartan (ARB). VEGF and TGF-beta1 protein and mRNA expression in RPMC were analyzed by ELISA and RT-PCR.


RESULTS
Glucose-containing PDS, even N 2.5% diluted twofold with M199 (which contains 1.25% glucose), increased VEGF and TGF-beta1 expression in RPMC (p < 0.05). Ex did not inhibit VEGF expression and did not inhibit TGF- beta1 expression after 24 h in RPMC. Pyridoxamine and ARB significantly reduced N 2.5%-induced VEGF and TGF-beta1 protein and mRNA expression in RPMC (p < 0.01).


CONCLUSIONS
Neither new pH-neutral, lactate-buffered, low-GDP, two-chamber bag PDS, nor 7.5% icodextrin PDS alone satisfactorily inhibited VEGF and TGF-beta1 overproduction in RPMC, but ARB or pyridoxamine effectively inhibited glucose-containing PDS (N 2.5%)-induced overproduction.
Mizuiri
Sonoo
S
Department of Nephrology, Toho University School of Medicine, Tokyo, Japan. sm210@med.toho-u.ac.jp
Ohashi
Yasushi
Y
Hemmi
Hiromichi
H
Arita
Michitsune
M
Yamada
Kanae
K
Aoki
Toshiyuki
T
Miyagi
Moriatsu
M
Sakai
Ken
K
Aikawa
Atsushi
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D015312:Hemodialysis Solutions; D008297:Male; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011733:Pyridoxamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D015312:Hemodialysis Solutions; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D011733:Pyridoxamine