Effect of valsartan versus lisinopril on peritoneal sclerosis in rats.
BACKGROUND
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.


METHODS
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.


RESULTS
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)


CONCLUSIONS
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.
Duman
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Department of Nephrology, Ege University, Izmir, Turkey. dumans@med.ege.edu.tr
Sen
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Duman
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Oreopoulos
D G
DG
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D005947:Glucose / Q000032:analysis; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D008853:Microscopy; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis; D013777:Tetrazoles / Q000494:pharmacology*; D014462:Ultrafiltration; D014508:Urea / Q000032:analysis; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000068756:Valsartan; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D000068756:Valsartan; D014508:Urea; D017706:Lisinopril; D014633:Valine; D005947:Glucose