Abstract 12859: Dietary Iron Restriction Attenuates Hypertension and Renal Injury in Aldosterone/Salt-Induced Hypertensive Mice
Backgroud: Excess iron is associated with the pathogenesis of several cardiovascular diseases. We have previously shown that dietary iron restriction (IR) prevents hypertensive cardiovascular remodeling in Dahl salt-sensitive hypertensive rats. However, it has not been investigated the effects of IR on hypertensive renal injury. The aim of this study is to investigate the effects of dietary IR on the development of hypertension and renal injury in aldosterone/salt-induced hypertensive mice.
Methods and Results: Ten-week-old male C57BL/6J mice (25-27g) were uninephrectomized and infused aldosterone (0.15μg/hr) with osmotic minipumps for 4 weeks. Aldosterone-infused mice were divided into 2 groups; fed a high-salt diet (Aldo, n=8) or fed a high-salt with iron-restricted diet (Aldo-IR, n=8). Saline-infused mice given a normal diet were served as controls (Control, n=6). Aldo mice showed progressive increase in systolic blood pressure compared with Control mice (114±8 vs 146±4mmHg, p≤0.05), while it was suppressed in Aldo-IR mice (146±4 vs 119±5mmHg, p≤0.05). Urinary albumin/creatinine ratio was increased in Aldo mice compared with Control mice (35.7±7.1 vs 361.5±67.7μg/mg, p≤0.05), which was attenuated by IR (361.5±67.7 vs 162.9±34.6μg/mg, p≤0.05). Moreover, urinary 8-Hydroxydeoxyguanosine/creatinine ratio was markedly increased in Aldo mice compared with Control mice (9.4±0.6 vs 20.8±2.1μg/mg, p≤0.05), whereas its ratio was decreased by IR (20.8±2.1 vs 13.7±1.1μg/mg, p≤0.05). In addition, renal histology revealed that Aldo mice exhibited glomerulosclerosis and tubulointerstitial fibrosis. In contrast, these histological changes were attenuated in Aldo-IR mice compared with Aldo mice. Interestingly, Western blot analysis showed that the renal expression of transferrin receptor 1 (TfR1), which is iron transport protein, was up-regulated in Aldo mice compared with Control mice. Immunohistochemistry further showed that TfR1 was expressed in the renal tubules in Aldo mice.
Conclusion: Dietary iron restriction attenuated the development of hypertension and renal injury in aldosterone/salt-induced hypertensive mice. Dysregulation of renal iron transport may be involved in the mechanism of salt-sensitive hypertension.
- © 2013 by American Heart Association, Inc.