Administration of angiotensin II induces iron deposition and upregulation of TGF-β1 mRNA in the rat liver

We previously found that angiotensin II infusion into rat causes iron deposition in the kidney and heart, which may have a role in the regulation of profibrotic genes expression as well as tissue fibrosis. In the present study, we have investigated whether angiotensin II can also induce iron accumulation in the liver. Prussian blue staining detected frequent iron deposition in the interstitium of the liver of rats treated with pressor dose angiotensin II for 7 days, whereas iron deposition was absent in the livers of control rats. Immunohistochemical and histological analyses showed that some iron-positive nonparenchymal cells were positive for ferritin and heme oxygenase-1 (HO-1) protein, and TGF-β1 mRNA, and were judged to be monocytes/macrophages. It was shown that angiotensin II infusion caused about a fourfold increase in ferritin and HO-1 protein expression by Western blot analysis and about a twofold increase in TGF-β1 mRNA expression by Northern blot analysis, which were suppressed by treating angiotensin II-infused rats with losartan and deferoxamine. In addition, mild interstitial fibrosis was observed in the liver of rats that had been treated with pressor dose angiotensin II for 7 days or with non-pressor dose angiotensin II for 30 days, latter of which also caused loss of hepatocytes and intrahetatic hemorrhage in the liver. Taken together, our data suggest that angiotensin II infusion induces aberrant iron homeostasis in the liver, which may have a role in the angiotensin II-induced upregulation of profibrotic gene expression in the liver.