The Effects of Systemic Infusion of Bradykinin on Experimental Peritoneal Fibrosis

Abstract

Background. Bradykinin (BK) is a proinflammatory peptide that is involved in the inflammation and vascular regulation. Recent studies have indicated that stimulation of BK-B2 receptors may attenuate fibrosis in renal and liver injuries and it is also expressed on neutrophils.Objectives. The aim of this study is to investigate the expression of bradykinin-B2 receptors and to explore the effects of systemic infusion of bradykinin (BK) using histochemical and immunohistochemical methods in a rodent model of chlorhexidine gluconate-induced peritoneal fibrosis.Materials and Methods. In this experimental study, twenty-four male SpragueDawley rats (n=24) were divided into three groups; Control, Chlorhexidine Gluconate (CG) and Chlorhexidine Gluconate+Bradykinin treatment (CG+BK). All animals were euthanized at day 21 and peritoneal tissue samples were taken under anesthesia induced by 50 mg/kg s.c. sodium pentothal. Histological assessments were then performed using hematoxylin and eosin, Periodic Acid-Schiff staining; and antibodies against TGF-β1, MMP-2, PAI-1 and bradykinin-B2 (BK-B2) receptors.Results. Thickness of submesothelial layer, neovascularization, polimorphonuclear granulocytes and fibrosis increased in the CG+BK treatment group. While expression of TGF-β1, MMP-2 and PAI-1 was not significantly different than that of the CG group. Staining of BK-B2 receptors was up-regulated in the submesothelial compact zone of the CG+BK treatment group.Conclusions. The results of our study showed that the stimulation of BK-B2 receptors by systemic BK perfusion did not have any antifibrotic effects in the encapsulating peritoneal sclerosis rat models, and actually, it may even promote fibrosis by aggravating inflammation.