Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin

Abstract

Introduction: Nephrotic syndrome induced by adriamycin (ADR) is an experimental model of glomerulosclerosis in humans. The AT 1 receptor for angiotensin II (Ang II) is involved in the renal expression of the nuclear factor-kappa B (NF-ΚB) during this nephrosis. NF-ΚB is a transcription factor for proinflammatory effects of Ang II; however, there is no information about the role of this receptor in the renal proinflammatory events in ADR nephrosis. Materials and methods:To determine the role of Ang II in ADR nephrosis, Sprague-Dawley rats were treated with ADR (6 mg/kg iv). One ADR group received oral losartan treatment (15 mg/kg gavage) 3 days before ADR injection and then daily for 4 weeks, and the other group water. Animals were sacrificed at week 4 and renal macrophage infiltration, ICAM-1, superoxide anion (O 2 -) and Ang II expressions were analysed by indirect immunofluorescence and histochemical techniques. Results: ADR rats showed increased expression of ICAM-1, Ang II, O 2 -and macrophage infiltration, events that were diminished by losartan treatment. Ang II expression remained unaltered after antagonist treatment. Proteinuria was reduced after 3 weeks of treatment. Conclusions: These data suggest that Ang II plays a role in the inflammatory events during ADR-induced nephrosis, probably mediated by AT 1 receptors.

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

“…In our current study, and consistent with those reports, animals with ADR-induced nephrotoxicity showed overproduction of TOS; this effect was diminished by ACE and/or renin inhibitors, suggesting an antioxidant effect of those inhibitors, probably due to the inhibition of an Ang-II NAD(P)H oxidase inducer effect with further decreased production of TOS. 36 Another possibility of this inhibitor's effect on decreased TOS might be that the nephrotic state as such reduced the bradykinin-induced endothelium-dependent increase in coronary flow and enhanced the aortic constrictor response to Ang-II associated with a reduced basal NO release, as apparent from the comparison of Adriamycin nephrotic rats. 37 It has been observed that there is a large accumulation of ADR in kidney than in any other organ.…”

Renal oxidative stress and renal CD8+ T-cell infiltration in mercuric chloride-induced nephropathy in rats: role of angiotensin II

“…Therefore, when the anti-Ang II treatment is given 3 days after HgCl 2 injection, it may be acting after the initiation of renal cellular injury. Muñoz et al (2011) showed that use of this anti-Ang II pre-treatment (3 days before and then throughout the experimental period) protocol diminished the expression of Ang II and pro-inflammatory molecules in an Adriamycininduced nephrosis model. The specific dose of HgCl 2 (2.5 mg/kg) and evolution time (96 h) used here were selected based on the fact that: (1) doses ranging from 1.0-3.5 mg HgCl 2 /kg induce dose-dependent alterations in the cytoplasm and nucleus of proximal tubular cells in rats (Stacchiotti et al 2003); and (2) important inflammatory events are seen 2-6 days post-exposure (Ghielli et al 2000).…”

“…Rats with no HgCl 2 treatment (Groups IV, V and VI) received, respectively, Enalapril, Losartan or normal saline only daily by gavage (500 ml). The Anti-Ang II doses used here were previously shown to be capable of diminishing pro-inflammatory events in different inflammatory models (Vargas et al 2012;Muñoz et al 2011;Peña et al 2012).…”

“…With the advent of drugs such as Losartan that specifically blocks the Ang II AT-1 receptor and Enalapril that blocks ACE activity, it is possible to dissect the physiological roles of the renin-angiotensin system (Abdi & Johns 1997;Donmez et al 2002;Benigni et al 2010;Muñoz et al 2011;Peña et al, 2013). Therefore, the aim of this study was to determine the role of Ang II in the renal oxidative stress and CD8 cell infiltration in rats treated with HgCl 2 using the angiotensin II receptor (AT-1) blocker Losartan and the ACE inhibitor Enalapril.…”

Sympathetic and Renin–Angiotensin Activity in the Pathophysiology of Hypertension

“…Infusion of Ang II in mice results in increased NOX activity, increased expression of proinfl ammatory cytokines and fi brosis-associated genes (such as α-smooth muscle actin, TGF-β, procollagen type I-α1), and increased levels of collagen I, with histological evidence of tubulointerstitial fi brosis [ 72 ]. In animal models of glomerular disease, Ang II induces oxidative stress, expression of adhesion molecules, macrophage infi ltration, and exacerbation of proteinuria [ 73 ]. These effects were also shown to be mediated by AT 1 R and prevented by AT 1 R blockade.…”