Duman S, Sen S, Duman C, Oreopoulos D G
Department of Nephrology, Ege University, Izmir, Turkey.
Int J Artif Organs. 2005 Feb;28(2):156-63. doi: 10.1177/039139880502800212.
Peritoneal sclerosis (PS) is one of the most serious causes of failure in long-term peritoneal dialysis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. We previously showed that ACE inhibitors (ACEIs) have beneficial effects on hypertonic PD solutions (3.86% PD) induced peritoneal alterations. The aim of this study is to compare the effects of an ACEI and a receptor blocker on peritoneal alterations induced by hypertonic PD solutions in rats.
Forty-three non-uremic rats were divided into four groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n = 10) and groups III and IV received hypertonic PD solution (10 ml/day) plus 640 mg/L valsartan (n=11) and 100 mg/L lisinopril in drinking water (n = 11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGFbeta 1 and VEGF levels were determined.
Administration of valsartan or lisinopril resulted in preserved UF (8+/-0.8 and 6.7+/-0.7 vs 4.9+/-0.8 mL), D1/D0 glucose (0.69+/-0.05 and 0.62+/-0.05 vs 0.56+/-0.04) and peritoneal thickness (19.4+/-2.9 and 28.5+/-5.2 vs 53+/-3 microm), respectively. Both higher level of TGF beta 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group. Both cytokines are partially inhibited by valsartan or lisinopril (p >0.05)
Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of valsartan or lisinopril led to attenuation of these alterations. We suggest that the equal protection of the peritoneal membrane from the effects of hypertonic glucose was achieved by receptor blockers and ACE inhibitors.
腹膜硬化（PS）是长期腹膜透析失败的最严重原因之一。已知血管紧张素II可促进各种组织中的纤维化和炎症。我们之前表明，血管紧张素转换酶抑制剂（ACEI）对高渗腹膜透析液（3.86%腹膜透析液）诱导的腹膜改变具有有益作用。本研究的目的是比较一种ACEI和一种受体阻滞剂对高渗腹膜透析液诱导的大鼠腹膜改变的影响。
43只非尿毒症大鼠分为四组：I组（假手术组）大鼠未接受治疗（n = 11），II组接受高渗（3.86%，10 ml/天）腹膜透析液（n = 10），III组和IV组接受高渗腹膜透析液（10 ml/天）加饮用水中640 mg/L缬沙坦（n = 11）和100 mg/L赖诺普利（n = 11）。四周后，用3.86%腹膜透析液进行1小时的腹膜平衡试验（PET）。测定透析液与血浆尿素比值（D/P尿素）、葡萄糖重吸收（D1/D0葡萄糖）、超滤量（UF）、透析液蛋白、转化生长因子β1（TGFβ1）和血管内皮生长因子（VEGF）水平。
缬沙坦或赖诺普利给药导致超滤量得以保留（分别为8±0.8和6.7±0.7 vs 4.9±0.8 mL）、D1/D0葡萄糖（0.69±0.05和0.62±0.05 vs 0.56±0.04）和腹膜厚度（19.4±2.9和28.5±5.2 vs 53±3微米）。葡萄糖组透析液中TGFβ1水平较高（206±40 vs 474±120 pg/mL，p<0.05），VEGF水平也较高（4±0.4 vs 7.9±3 pg/mL，p>0.05）。两种细胞因子均被缬沙坦或赖诺普利部分抑制（p>0.05）。
暴露于高渗葡萄糖溶液导致腹膜转运改变，表现为葡萄糖梯度迅速消散以及由此导致的超滤反应受损。缬沙坦或赖诺普利给药导致这些改变减轻。我们认为，受体阻滞剂和ACEI对腹膜免受高渗葡萄糖影响具有同等保护作用。
