Effect of Valsartan versus Lisinopril on Peritoneal Sclerosis in Rats

Abstract

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 (D1/D0 glucose), ultrafiltration volume (UF), dialysate protein, TGFß1 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 μm), respectively. Both higher level of TGF ß1 (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) Conclusion 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.

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

“…18,41 A number of medications, including valsartan, lisinopril, enalapril, octreotide, dipyramidole, and pentoxyphyline, were used to preserve longevity of PD yielding some degree of success. [9][10][11]37,48 There is only one report concerning the effects of atorvastatin. 49 In this study, atorvastatin was chosen to test its effects on the development of peritoneal fibrosis and to consider possible pathogenetic mechanisms using the aforementioned experimental model, 48 because of antioxidant, anti-inflammatory, [50][51][52] antiproliferative, atherosclerotic plaque stabilizing, anticoagulant, and renoprotective [53][54][55] effects of statins, independent of their lipid-lowering effects.…”

“…[1][2][3][4][5][6][7][8] To eliminate the deleterious effects of long-term PD on peritoneal function and structure, many agents including valsartan, lisinopril, enalapril, and octreotide were tried yielding some beneficial outcomes. [9][10][11] Statins are generally prescribed to treat hyperlipidemia; however, data concerning anti-inflammatory, antiproliferative, and antioxidant effects of statins are accumulating. [12][13][14][15][16] In this study, we aimed to test the effects of atorvastatin on peritoneal functions and peritoneal histology in rats on PD in terms of the pathogenesis.…”

No need for an “expiry date” in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis

“…This is only an indirect indication for the widespread use of these new solutions as a means to prevent EPS, but it seems more promising than a misunderstood precautionary principle. The inhibition of renin-angiotensin system should also be considered as the elective therapy of hypertension in PD patients since a number of papers [37][38][39] clearly indicate a role of ACE-inhibition in preventing peritoneal fibrosis.…”

Role of Spironolactone Chalcone in the Prevention of Peritoneal Fibrosis in Patients with Peritoneal Dialysis

“…It is reported that the peritoneal membrane damage is however prevented by angiotensin convertingenzyme inhibitors and angiotensin II receptor blockers [9][10][11]. There is improvement in prognosis of kidney injury patients using mineralocorticoid receptor antagonist [12,13].…”