Role of adhesion molecules in the progression of peritoneal sclerosis.
To investigate the role of adhesion molecules [intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and integrin alpha 5 beta 1] in the progression of encapsulating peritoneal sclerosis (EPS) under peritoneal dialysis, we examined changes in the expression of those adhesion molecules in Wistar-Kyoto (WKY) rats treated with acidic dialysis solution with or without angiotensin II type 1a receptor blocker (ARB). We divided 48 WKY rats into 4 groups and dialyzed them with various solutions as follows: (1) pH 7 1.5% glucose dialysis solution (control group, n = 12); (2) pH 3.5 1.5% glucose dialysis solution (EPS group, n = 12); (3) pH 3.5 1.5% glucose dialysis solution, plus oral administration of CS866 5 mg/kg daily (ARB group, n = 12); and (4) pH 3.5 1.5% glucose dialysis solution, plus oral administration of amlodipine (CA group, n = 12). We injected the dialysis solutions into the abdominal cavity and administered the ARB and CA daily for 42 days. On days 3, 7, 14, and 42, three rats in each group were humanely killed by decapitation, and we studied the expression of adhesion molecules in peritoneum by the immunofluorescence method. In the EPS rats, expression of adhesion molecules was observed in peritoneum on day 3 after start of acidic solution treatment, in conjunction with an increment of interleukin 6 (IL-6) in the dialysate. The peritoneum of EPS rats showed peritoneal fibrosis with interstitial cell infiltration. Treatment with ARB significantly suppressed expression of adhesion molecules in the peritoneum and suppressed peritoneal fibrosis. Treatment with a neutral solution induced no peritoneal fibrosis nor expression of adhesion molecules in the peritoneum. Our results suggest that adhesion molecules play an important role in the progression of peritoneal fibrosis and resultant EPS. Treatment with ARB prevents the progression of peritoneal fibrosis and suppresses expression of adhesion molecules in the peritoneum.
Imai
Hiroe
H
Department of Nephrology, Saitama Medical School, Saitama, Japan.
Nakamoto
Hidetomo
H
Fukushima
Rie
R
Ishida
Yuji
Y
Yamanouchi
Yasuhiro
Y
Suzuki
Hiromichi
H
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D015314:Dialysis Solutions / Q000737:chemistry; D018450:Disease Progression; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D000068557:Olmesartan Medoxomil; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011921:Rats, Inbred WKY; D012598:Sclerosis; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D015815:Cell Adhesion Molecules; D015314:Dialysis Solutions; D007093:Imidazoles; D015850:Interleukin-6; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil