The effect and mechanism of aldosterone receptor blocker and angiotensin-converting enzyme inhibitor on peritoneal fibrosis

Objective To investigate the effect and mechanism of aldosterone receptor blocker and angio- tensin-converting enzyme inhibitor on peritoneal fibrosis. Methods Fifty male Wistar rats were randomly divided into 5 groups. Group A (n = 10) was the control group, and groups B, C, D and E (n = 10 / each group) were treated with intraperitoneal injection of 20 ml 4.25% Beter dialysate daily. On days 1, 3, 5 and 7, rats were given intraperito- neal injection of lipopolysaccharides (LPS) 0.6 mg/kg/day. Group B (n=10) was used as the model of peritoneal fibrosis. Rats in group C were given angiotensin-converting enzyme inhibitor 10 mg/kg/day by gastric gavage in the morning once a day. Rats in group D were treated with aldosterone receptor blocker 100 mg/kg/day by gastric gavage once a day. Those in group E were treated with angiotensin-converting enzyme inhibitor as well as aldosterone receptor blocker. Rats were sacrificed after the treatment for 30 days. Their parietal peritoneum was stained with HE and Masson methods. In the peritoneal dialysate fluid from rat abdominal cavity, total cells and macrophage cells were counted, and TGF-a in the fluid was measured. MCP-1 and C-JUN/AP-1 were examined in peritoneal mesothe- lial cells by immunohistochemical staining. Results Less pathological changes in peritoneum and low TGF-a in the dialysate were found in the treated groups (groups C, D and E) than those in the untreated group (group B). The expression of MCP-1 was found in peritoneal mesothelial cells as well as in the endothelial cells on capillary and small veins. Group E showed less peritoneal fibrosis, lower number of macrophages in the dialysate, and lower expression of MCP-1 and C-JUN/AP-1 in peritoneal mesothelial cells. Conclusions Aldosterone receptor blocker in combination with angiotensin-converting enzyme inhibitor effectively inhibited peritoneal fibrosis by the inhibition of inflammation reaction and fibrosis processes. This effect may be related to the decrease level of MCP-1 and C-JUN/ AP-1 in peritoneal mesothelial cells and the inhibition of TGF-a and MCP-1 expression.