Pro-inflammatory role of angiotensin II in mercuric chloride-induced nephropathy in rats.

Mercuric chloride (HgCl₂), which induces kidney toxicity, constitutes a potential threat to human health. In addition to direct toxic effects, kidney inflammatory events take place during the HgCl₂-induced nephropathy. There is no information currently available about the role of angiotensin II (Ang II) in this inflammatory process. Accordingly, the aim of this study was to determine the expression of Ang II and Ang II-associated inflammatory molecules, i.e. intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS), and mono-cyte/macrophage infiltration (ED-1), in HgCl₂-induced nephropathy. Three groups of Sprague Dawley rats that were to receive HgCl₂ (2.5 mg HgCl₂/kg BW, by gavage) were utilized: one had received Losartan at 30 mg/kg BW; one had received Enalapril at 30 mg/kg BW; and one had received distilled water, in each case daily for 3 days prior to the HgCl₂ exposure. For these studies, an extra set of controls treated with saline solution in place of HgCl₂ and water in place of the test drugs was employed. Renal biopsies were obtained 96 h after HgCl₂ injection and the expressions of Ang II, ICAM-1, iNOS, and ED-1 were analyzed by indirect immunoflourescence while tubular damage was assessed via histopathology. An increased expression of Ang II, ICAM-1, iNOS, and ED-1 as well as increases in tubular necrosis were observed in all HgCl₂-animals. Treatments with Losartan or Enalapril diminished the induced expressions as well as the extent of tubular damage. The data here suggest that Ang II is involved in the pro-inflammatory events during HgCl₂-induced nephropathy, and that this is probably mediated, in part, by Ang II receptors Type 1 (AT-1).