Role of the renin-angiotensin system in the pathogenesis of peritoneal fibrosis.
BACKGROUND
Although the effects of angiotensin type 1 receptor blocker (ARB) have been studied, little is known about ARBs in hypertensive patients undergoing dialysis. In the present study, we evaluated the effect of an ARB, olmesartan medoxomil (CS866), on the progression of peritoneal fibrosis in peritoneal dialysis by examining its effect in a model of peritoneal fibrosis in hypertensive rats.


METHODS
We allocated 40 male Wistar rats with 2-kidney, 1-clip renovascular hypertension (2K1C-RVH) to 4 groups (each n = 10) that were dialyzed using various solutions for 42 days as follows: Group I-10 mL pH 3.5 dialysis solution containing 1.35% glucose Group II-10 mL pH 3.5 dialysis solution, plus oral administration of CS866 5 mg/kg daily Group III-10 mL pH 3.5 dialysis solution, plus oral administration of the calcium channel blocker (CCB) amlodipine 3 mg/kg daily Group IV-10 mL pH 7.0 dialysis solution Dialysis solution was injected every day for 42 days.


RESULTS
Treatment with CS866 and amlodipine induced a significant reduction of blood pressure in 2K1C-RVH rats. In rats treated with pH 3.5 dialysis solution, necropsy findings revealed features identical to those of encapsulating peritoneal sclerosis (EPS). The typical appearance was multiple surfaces covered with granulation tissue or fibrosic tissue or both. Multiple adhesions were present. Microscopic findings revealed that acidic dialysis solution induced peritoneal fibrosis and loss of mesothelium. Treatment with CS866 prevented the progression of peritoneal fibrosis and adhesions. However amlodipine did not improve the progression of peritoneal fibrosis and peritoneal adhesions. In CS866-treated rats, no signs of EPS were present.


CONCLUSIONS
Long-term intraperitoneal exposure to acidic dialysis solution produced features typical of EPS. Acidic dialysis solution induces activation of the peritoneal renin-angiotensin system and progression of peritoneal fibrosis. For the peritoneum undergoing peritoneal dialysis, ARB protects against progression of peritoneal fibrosis and peritoneal adhesions.
Department of General Internal Medicine, Saitama Medical School, Saitama, Japan. nakamo_h@saitama-med.ac.jp
Hidetomo
H
Nakamoto
Hiroe
H
Imai
Rie
R
Fukushima
Yuji
Y
Ishida
Yasuhiro
Y
Yamanouchi
Hiromichi
H
Suzuki
D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015314:Dialysis Solutions / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D006863:Hydrogen-Ion Concentration; D006978:Hypertension, Renovascular / Q000150:complications; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D000068557:Olmesartan Medoxomil; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000209:etiology* / Q000517:prevention & control*; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015314:Dialysis Solutions; D007093:Imidazoles; D013777:Tetrazoles; D017311:Amlodipine; D000068557:Olmesartan Medoxomil